Biomarkers of Exposure and Effect in Standardized Research E-cigarette (SREC) Users: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Biomarkers of Exposure and Effect in Standardized Research E-cigarette (SREC) Users (NCT04003805), a na phase 1 study. The primary outcome is Exposure Biomarkers: Cotinine.

2. Clinical Question

3. Trial Design

This Phase 1 study is registered as a single-group study with no masking and no allocation to comparative arms. Its listed enrollment is 47. The registry describes a group switching from smoking cigarettes to SREC, rather than separate groups assigned to SREC and a control intervention. That structure matters when interpreting the primary endpoint: cotinine after switching is expressed relative to baseline, not as a randomized contrast between treatments.

The study is marked completed. Its recorded start date is 2022-05-11 and its primary completion date is 2024-05-31. The sponsor is Masonic Cancer Center, University of Minnesota. The registry record does not give further details about recruitment, participant eligibility, the timing of assessments other than the primary endpoint timeframe, or the conduct of the study visits.

The primary outcome is Exposure Biomarkers: Cotinine. It is described as cotinine level after switching to SREC, expressed as a percentage of baseline level, with a timeframe of 6 weeks. The record also lists secondary outcomes concerning product use, cigarette avoidance, total NNN, and 8-oxo-dG DNA adduct. It records 10 outcome measures overall, but does not provide results for the primary endpoint in the information.

Because this is a single-group study, its design can characterize measurements associated with switching and compare a post-switch measure with a baseline reference. It does not provide a randomized, concurrent control comparison. The record does not report a protocol, a statistical analysis plan, or details of how the enrollment was selected or justified.

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 Exposure Biomarkers: Cotinine, measured over 6 weeks.

The primary endpoint is cotinine, identified in the registry as a biomarker of nicotine. The outcome is defined as the cotinine level after switching to SREC, expressed as a percentage of the baseline level, at 6 weeks. The stated summary measure is the mean, and the stated dispersion measure is the standard deviation.

Using a percentage of baseline places the post-switch measure in relation to each participant’s starting level. In general, a biomarker can provide a measurable indicator of exposure; cotinine is relevant because it reflects nicotine exposure. The mean describes the central value across the observations included in an analysis, while the standard deviation describes variability among those observations. These summaries do not, by themselves, establish why a level changed or what the change means for other exposures or health effects.

The registry record does not report the observed cotinine mean, standard deviation, confidence interval, or analysis population. It therefore does not show the magnitude or precision of the primary endpoint result. Cotinine is one exposure measure and should not be treated as a complete measure of the toxic or carcinogenic potential that motivated the study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the mean describe?

The primary outcome is a continuous measurement summarized by a mean. In general, a mean describes the central value of the observations included in an analysis. It is not a description of every participant’s value, and it can be affected by the distribution of individual measurements. The registry record specifies the mean as the primary summary but does not report the observed mean or define the analysis population used to calculate it.

The outcome is expressed as a percentage of baseline. This puts the post-switch cotinine measure in relation to a baseline level rather than presenting it as an absolute concentration. The record does not explain the calculation details or say whether the percentage is calculated for each participant before averaging. Those details are not reported in the registry record and should not be inferred from the outcome description alone.

What does the standard deviation add?

The standard deviation is the stated measure of dispersion. As a general statistical concept, it describes how spread out individual observations are around the mean. It does not describe the precision of the estimated mean. A broad spread among participants and uncertainty about the mean are related but different ideas: the latter depends on the analysis and the amount of usable information, among other factors. The registry record does not report the cotinine standard deviation, so the observed variability cannot be assessed.

How would uncertainty be assessed?

In general, a confidence interval gives a range of values compatible with the data and the method used to estimate it. Its width helps communicate precision, while its location describes the values supported by that analysis. A confidence interval is not reported for the primary cotinine endpoint in the registry record. The record also lists no analyses, so it does not specify an inferential method, a standard error, or a hypothesis test for this endpoint. There is therefore no reported statistical evidence from which to assess the precision or statistical significance of the primary result.

Because the study is single-group, the baseline reference does not create an independent treatment comparison. A within-person or baseline-referenced analysis can account for the fact that measurements are linked to the same participant, but the record does not state which analysis was used. A general comparison of before-and-after measurements also cannot rule out time-related influences or other explanations for change without an appropriate design and analysis.

What can the planning assumptions tell us?

The planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also describes planning to detect a stated fraction of an observed effect. For time-to-event calculations, the stated convention is a total event count; for other calculations, it is participants per arm. These assumptions describe a planning framework, not observed study results.

That framework does not change the registered design: the study is recorded as single-group, with allocation not applicable. A hypothetical two-arm planning calculation should not be read as evidence that the study enrolled or compared two randomized arms. The record does not provide a sample-size justification or the numerical planning results, and those details are not reported in the registry record. Planning illustrations are not observed power and cannot establish what the completed study was able to detect.

Why does the outcome’s scale matter?

Cotinine is a continuous biomarker, and a mean with standard deviation is a familiar way to describe such a measure. In general, interpretation also depends on the distribution of values, the handling of unusual observations, and whether the summary is appropriate for the data. The registry record does not report diagnostic checks, transformations, or alternative summaries. It would be inappropriate to assume that any particular modeling choice was made.

General statistical methods should match the type of outcome and the study design. For example, over-dispersion is a concern for some count-data models when observed variability exceeds what a model assumes; it is not a direct description of a continuous cotinine mean. The record does not describe a count model for the primary endpoint. The serious-event counts are safety observations, not a reason to infer a particular model for cotinine.

For this study, the available methods information establishes the outcome scale, summary measure, dispersion measure, and timeframe. It does not establish how missing measurements were handled, which participants were included in each analysis, whether covariates were used, or how uncertainty was calculated. Those analysis details are not reported in the registry record.

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("Switching From Smoking Cigarettes to SREC")
n   <- c(23)
m   <- c(98.5)
sp  <- c(51.1)
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  Switching From Smoking Cigarettes to SREC  23  98.500  51.100  76.403  120.597

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures overall. It identifies cotinine as the primary outcome and names secondary outcomes concerning product use, cigarette avoidance, total NNN, and 8-oxo-dG DNA adduct. When a study assesses multiple outcomes, the chance of at least one apparently unusual finding can increase if many separate statistical tests are performed. General approaches to this issue include prespecifying a primary endpoint or adjusting inference across tests. The registry record does not report a multiplicity strategy, and it lists no analyses.

The record does not report whether any endpoint results were missing, how missing measurements were handled, or whether any imputation or sensitivity analysis was performed. It also does not report a statistical analysis population or state which participants contributed to each outcome. The listed enrollment is not enough to determine how many participants had usable measurements for the primary endpoint.

Details of interim analyses and the statistical analysis plan are not reported in the registry record. Without those details, it is not possible to establish how the analysis handled multiple outcomes, missing data, or deviations from any planned methods. These are reporting gaps, not evidence that a particular procedure was or was not used.

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: thromboembolic event (dvt/pulmonary embolism) (2.1%), cancer, lung (2.1%), head injury - accident (2.1%), pneumonitis (pneumonia) (2.1%), cardiomyopathy (2.1%).

The safety record lists 47 participants at risk for serious adverse events, with 5 affected, and 47 at risk for other adverse events, with 28 affected. It records 0 deaths. These figures describe the posted safety counts for the switching group; they do not compare SREC with a separate control group.

The serious-event terms listed are thromboembolic event (DVT/pulmonary embolism), cancer, lung; head injury - accident; pneumonitis (pneumonia); and cardiomyopathy. Each is accompanied by 2.1% in the registry record. These terms are descriptions of reported events, not proof that the intervention caused them. The record does not report a causal attribution or a comparative safety analysis.

Counts of affected participants and event terms should be read as different kinds of information: an event category may not correspond to a separate person, and the record does not provide further detail about overlap or timing. The figures alone do not establish a rate relative to another treatment or to usual experience. Additional safety context and methods are not reported in the registry record.

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

The record establishes that the study examined smokers switching to SREC and defined cotinine as its primary exposure biomarker. It specifies a mean percentage of baseline at 6 weeks, with standard deviation as the dispersion measure. However, it does not report the observed cotinine result or its uncertainty. The record therefore does not show whether the mean was higher or lower than baseline, how large any difference was, or how precisely it was estimated.

The single-group design permits description of measurements associated with switching and comparison with a baseline reference. It does not provide a randomized concurrent control contrast. A baseline-referenced change cannot by itself distinguish the effect of switching from other influences over time. The registry record does not report an analysis that addresses this limitation.

Cotinine is a biomarker of nicotine, not a complete measure of all chemical exposures, biological effects, or potential health outcomes. The record lists other exposure and effect outcomes, but their results are not reported in the information described. The study’s stated aim of generating initial reference data should not be mistaken for a definitive evaluation of e-cigarettes as tobacco risk reduction tools.

The posted safety figures describe events recorded in the switching group, but without a concurrent control group they do not estimate comparative safety. They also do not, on their own, establish whether an event was caused by SREC. The record supports a description of the registered design and outcomes, but not a conclusion that the intervention does or does not work or that it changes health risk.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a clearly defined endpoint and a reported result. The registry identifies cotinine, its interpretation as a nicotine biomarker, its percentage-of-baseline scale, and its 6-week timeframe. Yet the numerical endpoint result is not reported in the registry record. Without the estimate and a measure of uncertainty, readers cannot judge the magnitude, direction, or precision of the primary finding.

The single-group structure also matters statistically. A baseline reference can support a description of change, but it does not provide the same protection against alternative explanations as a randomized concurrent comparison. The design should therefore shape the claims made from any observed difference. In this record, the lack of a reported cotinine result further limits interpretation.

The study’s purpose is to generate initial reference data on exposure and associated effects during switching to a standardized research e-cigarette. That purpose makes clear outcome definitions and complete reporting especially important: reference values are useful only when readers can see what was measured, how it was analyzed, and how uncertain the result is. The registry lists multiple outcomes and safety observations, but does not report the corresponding analyses.

For biostatisticians and clinical researchers, this record is a useful reminder to separate study design, outcome specification, numerical results, and causal interpretation. A registered endpoint is not itself evidence of an effect, and planning assumptions do not substitute for observed estimates.

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.

The registry record does not report the primary cotinine estimate, its standard deviation, a confidence interval, or a statistical test. Consequently, the endpoint’s magnitude, direction, variability, and precision cannot be assessed. The record also lists no analyses, leaving the analytical approach unclear.

The single-group, unmasked design has no separate randomized or concurrent control group. Comparisons to baseline can describe measurements over time but cannot, by themselves, distinguish switching-related changes from other time-related influences. The record does not describe adjustments that might address these issues.

Participant eligibility and characteristics beyond the description of smokers switching to SREC are not reported. The record does not provide details about adherence, product-use patterns, measurement procedures, or the analysis population. It also does not state how missing data were handled or whether results were available for all enrolled participants.

The primary endpoint is one biomarker of nicotine exposure. Although the study lists other exposure and effect outcomes, their results are not reported in the registry information described. The safety figures likewise lack a control comparison and do not establish causality. These limitations restrict the conclusions that can be drawn from the registry record; they do not establish what unreported analyses or protocol details may have contained.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Biomarkers of Exposure and Effect in Standardized Research E-cigarette (SREC) Users — NCT04003805.
• Registry record last updated 2026-10-15; status last verified 2026-10.
• Results first posted 2026-01-29.
• 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

NCT04003805 is a completed Phase 1, single-group study sponsored by Masonic Cancer Center, University of Minnesota. The study enrolled 47 participants and examined switching from cigarette smoking to the Standardized Research E-cigarette. Its recorded start date is 2022-05-11, and its primary completion date is 2024-05-31.

The primary outcome was cotinine, expressed as a percentage of baseline at 6 weeks and summarized as a mean with standard deviation. The registry lists secondary outcomes concerning product use, cigarette avoidance, total NNN, and 8-oxo-dG DNA adduct, with 10 outcome measures overall. It lists no analyses, and the primary cotinine result is not reported in the registry record.

The safety record lists serious and other adverse-event counts and 0 deaths. No separate control group is recorded, so the study does not supply a randomized comparative estimate.