The Effects of Sedatives on Tobacco Use Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effects of Sedatives on Tobacco Use Disorder (NCT03813121), a randomized phase 1, phase 2 study. The primary outcome is Side Effects.

2. Clinical Question

The trial title concerns effects of sedatives on tobacco use disorder. Its brief summary describes an aim to obtain preliminary data on cigarette craving, smoking behavior, tolerability, and acceptability after a single sub-anesthetic sedative dose. The posted primary outcome, however, is a side-effects score. The registry record does not post a primary outcome result for craving or smoking behavior in the information available for this analysis.

The central statistical question is therefore narrower than whether these infusions alter tobacco use. It concerns the reported average severity of a set of symptoms after infusion, and whether the posted information permits a reliable comparison between ketamine and placebo. The endpoint results are descriptive arm summaries; a contrast, uncertainty interval, and inferential test for that comparison are not reported. The record also lists midazolam as an intervention, but the primary outcome results contain only placebo and ketamine arms. The clinical question cannot be extended to a direct comparison involving midazolam on the basis of these posted results.

3. Trial Design

The registry identifies this study as phase 1 and phase 2, randomized, single-masked, and parallel. It is marked completed. The listed enrollment is 10. The study start date is 2019-06-01, and the primary completion date is 2021-08-31. The sponsor is Wake Forest University Health Sciences.

The interventions include intravenous infusions of midazolam, placebo, and ketamine. The arm descriptions specify a single midazolam infusion of 0.02 mg/kg over 20 minutes, a single saline placebo infusion over 20 minutes, and a single ketamine infusion of 0.5 mg/kg over 20 minutes. The record does not report who was masked, how assignment was generated or concealed, or other details of the allocation procedure. It identifies the model as parallel but does not describe the operational conduct of the masking.

The posted primary outcome data include a placebo arm with 4 participants and a ketamine arm with 6 participants. No midazolam result appears in the primary outcome results. The outcome was assessed about 1 week post infusion. The listed endpoint is a mean score on a side-effects scale, with standard deviation as the measure of spread.

The enrollment figure is a registry design characteristic; the arm-level counts describe the posted primary outcome data. The record does not explain the relationship between those counts and enrollment, nor does it report a sample-size justification. Details such as eligibility criteria, participant flow, protocol deviations, and reasons for any missing outcome data are not reported in the registry record. The design labels alone do not establish the analysis population or all features of the trial conduct.

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: Participants must be screened for eligibility before being assigned to a group. Participants deemed ineligible were excluded from the study.

Overall Study

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 Side Effects, measured over about 1 week post infusion.

The primary outcome is titled “Side Effects” and is measured as a score on a scale. The recorded measure uses a severity scale from 1 (not at all) to 7 (extremely) for nausea, dizziness, sleepiness, strange thoughts, hallucinations, confusion, anxiousness, and headache. The average score across all listed side effects is reported. The timeframe is about 1 week post infusion.

This composite summary is intended to describe the average reported severity across several symptoms, rather than the frequency of each symptom separately. A mean can give a compact description of the overall level of scores in an arm. The standard deviation describes how dispersed individual scores are around that arm’s mean; it is not a confidence interval for the mean and does not itself quantify the uncertainty in a comparison between arms.

The endpoint is relevant to tolerability because it captures symptom severity after an infusion. It does not, by itself, describe craving, smoking behavior, acceptability, or the clinical importance of any individual symptom. The registry record does not provide separate symptom-level results or define a threshold for interpreting a difference on the scale. It also does not report a primary endpoint result for midazolam.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean describe?

A mean is an average of the observed measurements in a group. For this outcome, it summarizes the side-effects scale scores for participants in an arm. The reported values are 1.3 for placebo and 1.4 for ketamine. A mean is useful for describing the group’s central score, but it does not reveal the full pattern of individual observations. Different sets of scores can have the same mean, and an average can conceal variation among symptoms or participants.

What does the standard deviation add?

The standard deviation describes how much the observations tend to vary around their group mean. The registry reports 0.2 for placebo and 0.7 for ketamine. A smaller standard deviation indicates scores more closely clustered around the mean; a larger one indicates more dispersion. This is a description of variability in the observed scores, not a measure of precision for a between-arm effect. It is also not a range containing a specified proportion of participants, and it is not a confidence interval.

Why is an arm comparison different from two arm summaries?

A comparative analysis estimates how the outcome differs between treatment groups, under a defined analysis approach. It may report an effect estimate and an uncertainty interval, and may also report a test of a statistical hypothesis. The registry record does not post such an estimate or test for the primary continuous outcome. Its stated reason is that values are missing or not estimable for a two-arm comparison. Thus, the two means can be described separately, but they do not substitute for a reported comparative analysis.

In general, a confidence interval is a range of values compatible with the data and the statistical assumptions used to construct it. Its width reflects uncertainty: wider intervals indicate less precision, while narrower intervals indicate greater precision. An interval for a difference would help readers assess both the direction and range of plausible effects. No comparison interval is available in this record, so the precision of a placebo-versus-ketamine effect cannot be evaluated from the posted results. This general explanation does not imply that any unreported interval can be reconstructed.

Why can small outcome groups limit precision?

In general, estimates based on limited numbers of observations can be sensitive to the scores of individual participants. That makes the observed mean and spread useful descriptions of the posted data but not a guarantee of precision about a broader population. The record reports 4 participants for placebo and 6 for ketamine, but does not provide participant-level scores, an interval, or details of the analysis population. Without those details, readers cannot examine the influence of individual values or evaluate how the result might vary under alternative analysis choices.

What is the role of the scale’s range?

The scale anchors run from 1, meaning “not at all,” to 7, meaning “extremely.” The values near the lower end describe relatively low average reported severity on this scale, but the record does not define a threshold for clinical importance or provide a minimally important difference. A numerical mean should therefore be interpreted according to the stated scale, not as a direct measure of overall safety, acceptability, or tobacco-use outcome. The composite also averages across several named symptoms, so it does not establish the severity or occurrence of any one symptom.

What is and is not reported about analysis choices?

The registry identifies the outcome statistic as a mean and the spread statistic as a standard deviation. It does not report a model, covariate adjustment, assumptions check, handling of outliers, confidence-interval method, or inferential test for this outcome. It also lists zero analyses. These omissions prevent a fuller assessment of how a comparative result would have been estimated. General statistical methods can clarify what such analyses ordinarily do, but they cannot establish which method this trial used when the record does not say.

For continuous outcomes, an analysis may compare group means, potentially accounting for design features or other prespecified variables. In general, model assumptions and the distribution of measurements matter to the validity and precision of an estimate. No information is reported about distributional checks or an alternative approach if assumptions were not met. The record’s arm summaries remain interpretable as descriptive results, but no method-specific claims about adjusted effects or robustness can be made.

Sample-size calculations used for planning are distinct from observed trial findings. The registry record does not report a sample-size justification for this study. Any planning illustration based on an observed effect would not be observed power, and would depend on assumptions about allocation, significance level, and the effect targeted. Such an illustration does not replace a confidence interval or an analysis of the trial data. The record does not report interim analyses or a statistical analysis plan.

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("Placebo Intravenous Infusion", "Ketamine Intravenous Infusion")
n   <- c(4, 6)
m   <- c(1.3, 1.4)
sp  <- c(0.2, 0.7)
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  Placebo Intravenous Infusion  4  1.300  0.200  0.982  1.618
CARM  Ketamine Intravenous Infusion  6  1.400  0.700  0.665  2.135

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and zero posted analyses. It does not report a multiplicity plan, such as how statistical testing would be handled across outcomes, treatment comparisons, or time points. Since a comparative test for the posted primary outcome is not reported, there is no posted p-value whose interpretation could be adjusted or assessed for multiplicity. The number of outcomes listed in the registry does not establish how many outcomes were collected or analyzed.

The primary outcome results give arm-level summaries for placebo and ketamine. The record does not report a midazolam result for this endpoint, and it does not explain why that arm’s result is absent. It also does not report participant-level missingness, reasons for missing values, imputation, or other missing-data methods. The stated limitation is that values are missing or not estimable for a two-arm comparison; the record does not clarify whether this reflects unavailable data, an analysis decision, or another reason.

The analysis population is not reported in the registry record. There is no stated description of whether the results use all randomized participants, only participants with observed outcome data, or another defined group. The listed arm counts describe the posted outcome summaries, but do not establish a population-analysis rule. The record also does not report protocol deviations or details about participant flow that would help interpret the counts.

In general, multiplicity matters because making many statistical comparisons can increase the chance of finding an apparently noteworthy result by chance. Missing data matter because conclusions can depend on why observations are absent and how the analysis handles them. Those are general statistical considerations, not claims that a particular adjustment or missing-data problem occurred in this trial. The registry does not provide enough information to assess either issue beyond the omissions described.

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 non-serious adverse event terms

The serious adverse event figures are reported separately from the primary side-effects score. In the placebo group, 4 participants were listed as at risk for serious adverse events and 0 were affected. In the ketamine group, 6 were listed as at risk and 0 were affected. Deaths are reported as 0 in both groups. No serious adverse event terms are listed.

These figures describe the registry’s posted serious-event counts. They do not establish that no symptoms or other adverse events occurred. The record separately lists other adverse events: 1 affected participant among 4 at risk in the placebo group and 3 affected participants among 6 at risk in the ketamine group. No specific terms for those other events are given in the registry record used for this analysis.

In general, an adverse-event count is not a measure of severity for every symptom, and an absence of reported serious events does not by itself settle broader safety questions. The record does not provide event-level detail, timing, duration, attribution, or a comparative safety analysis. These counts should therefore be read as registry-reported summaries, not as a complete description of all safety observations or as evidence about causation.

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

The posted primary results describe side-effects scores about 1 week after infusion for placebo and ketamine. They report means and standard deviations, with the placebo mean at 1.3 and the ketamine mean at 1.4. The registry does not report an estimable two-arm comparison, a confidence interval, or a statistical test for this endpoint. Accordingly, the results do not establish whether the arms differ, nor do they establish that they are equivalent.

The endpoint concerns average severity across nausea, dizziness, sleepiness, strange thoughts, hallucinations, confusion, anxiousness, and headache. It is not a direct measure of cigarette craving, smoking behavior, or the broader impact of tobacco use disorder. Although the study summary names craving, smoking behavior, tolerability, and acceptability as aims, the posted primary endpoint result addresses only the side-effects score. Separate symptom-level results are not reported.

The record also lists a midazolam intervention, but does not post its primary outcome result. Thus, the available endpoint summaries cannot answer how midazolam compares with placebo or ketamine. Nor can the results establish a general effect of sedatives as a class, since the record does not provide comparative outcomes for all listed interventions.

These results are descriptive and limited to the posted arms, endpoint, and assessment time. The registry does not report the analysis population, missing-data handling, or enough detail to evaluate the precision of a treatment contrast. The findings should not be interpreted as a definitive conclusion about efficacy, tolerability, safety, or tobacco-use outcomes. They show the reported arm-level score summaries and the limits of the comparative information available in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates a key distinction in clinical-trial reporting: arm-level descriptive statistics are not the same as an estimated treatment effect. Means and standard deviations communicate the observed score level and variability within each reported arm. A comparative estimate and its uncertainty would address a different question—how the outcome differs between interventions and how precisely that contrast is known. The registry record does not report that comparison for the primary continuous endpoint.

The case also shows why the outcome definition matters. A composite average across several symptoms can be useful as a concise tolerability measure, while still obscuring symptom-specific patterns. Without separate results, readers cannot tell whether the composite reflects similar levels across symptoms or a narrower subset. The scale anchors provide context for the score, but no threshold for clinical importance is reported.

Registry records can also expose gaps between the intervention list and the outcome results. Midazolam is listed as an intervention, yet the posted primary outcome summaries cover placebo and ketamine only. Making that distinction explicit prevents readers from assuming that every planned arm has a corresponding posted result.

Finally, the record demonstrates the importance of transparent information about analysis populations, missing data, and multiplicity. These details help readers understand which observations contributed to a result and how uncertainty should be interpreted. Their absence does not prove that a particular problem affected the trial; it limits what can be concluded from the registry record. A careful statistical reading therefore separates reported descriptive findings from comparative claims that are not documented.

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 primary endpoint results cover placebo and ketamine, but not the listed midazolam intervention. The registry does not explain the absence of a midazolam result or report whether that outcome was collected. The posted information therefore cannot support a three-intervention comparison for this endpoint.

The outcome is a composite average across several symptoms, and no symptom-specific results are reported. The scale is described with anchors from 1 (not at all) to 7 (extremely), but no interpretation threshold or minimally important difference is stated. The score’s assessment is about 1 week post infusion; other time points are not described in the posted primary outcome data.

The record provides group means and standard deviations but no estimable comparison, uncertainty interval, or inferential test. It does not report the analysis population, missing-data methods, participant flow, or reasons for any absent result. It also does not describe the statistical model, adjustment choices, or analysis assumptions. These omissions limit assessment of precision and robustness.

Additional design and population details are not reported in the registry record, including participant characteristics, eligibility specifics, who was masked, and the sample-size justification. The listed enrollment and arm-level outcome counts do not explain participant flow or establish the analysis set. The registry identifies the study as completed, but completeness of reporting for outcomes beyond the posted primary result cannot be established from this record alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The Effects of Sedatives on Tobacco Use Disorder — NCT03813121.
• Registry record last updated 2022-10-06; status last verified 2022-08.
• Results first posted 2022-06-02.
• 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

The registry record describes a completed, randomized, single-masked, parallel phase 1 and phase 2 trial sponsored by Wake Forest University Health Sciences. Enrollment is listed as 10. The study began on 2019-06-01, with primary completion on 2021-08-31. Interventions include intravenous midazolam, placebo, and ketamine.

The posted primary outcome is a mean side-effects score assessed about 1 week post infusion, with standard deviation reported as the measure of spread. Results are available for placebo and ketamine, but the record states that values are missing or not estimable for a two-arm continuous-outcome comparison. No comparative estimate or analysis is posted. Serious adverse event counts and deaths are reported as 0 in both posted groups. Analysis-population details, missing-data methods, and a sample-size justification are not reported in the registry record.