The Effect of Cycloserine on Smoking Behavior in Nicotine Dependent Smokers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effect of Cycloserine on Smoking Behavior in Nicotine Dependent Smokers (NCT00633256), a randomized na study. The primary outcome is Cigarettes Smoked Per Day.

2. Clinical Question

3. Trial Design

The registry describes a randomized study comparing cycloserine with matched placebo. It records the allocation as randomized, masking as triple, and the model as factorial. The brief summary calls the study double-blind. The record does not identify which people were masked, explain the factorial structure, or describe how any factors were assigned. Those design details are not reported in the registry record.

The planned study is described as a four week, between-groups, placebo-controlled experiment involving cue exposure. Participants were to attend two experimental sessions, separated by approximately one week. The summary says each experimental session would last approximately 4.5 hours, with follow-up sessions lasting approximately thirty minutes. It describes physiological measures, including heart rate, blood pressure, and skin conductance, and subjective measures such as smoking urges. The record lists the study status as completed and enrollment as 20.

The primary outcome is cigarettes smoked per day at the 1 week follow-up. The endpoint description specifies that the analysis population comprised participants who completed the 4-week follow-up timepoint. The reported arms each have n=8.0. The record does not explain the relationship between the 1 week outcome timepoint and the stated completion criterion, or provide participant flow by group.

The summary describes additional aims involving smoking cue reactivity, smoking behavior, memory performance, and safety and tolerability. The registry also lists urinary cotinine as a secondary outcome. The primary endpoint summaries are descriptive; no analysis result for a between-group comparison is posted.

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

Analysis population for the primary outcome, as defined in the registry: The number of participants used for analysis were those who completed the 4-week follow-up timepoint.

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 Cigarettes Smoked Per Day, measured over 1 week follow-up.

The primary endpoint is cigarettes smoked per day at the 1 week follow-up. Its description defines the measure as the number of cigarettes smoked per day at that timepoint. The unit is cigarettes per day, and the reported summary measure is the mean with standard deviation. The registry says the analyzed participants were those who completed the 4-week follow-up timepoint.

In general, a cigarette-per-day measure is a direct way to describe reported smoking behavior over a defined period. It can express the outcome in units that are familiar and readily interpretable, while a mean summarizes the group’s average and a standard deviation describes variability among individual observations. The registry summary also identifies self-reported smoking and saliva cotinine as measures related to its smoking-behavior aim. Urinary cotinine is listed as a secondary outcome. These are distinct measurements; the primary endpoint is cigarettes smoked per day, not a cotinine concentration.

The record gives a timeframe and a completer-based analysis description, but does not report the specific recall procedure used to obtain the cigarette count, the handling of unusually high or low values, or whether any transformation was considered. The primary outcome summaries therefore describe the posted measure as defined in the registry, without clarifying those collection and analysis details.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary-outcome summaries use the mean and standard deviation for a continuous measure. The mean describes the average cigarettes-per-day value among the participants included in each arm’s summary. The standard deviation describes how dispersed the individual observations are around that arm’s mean. These are descriptive statistics. By themselves, they do not test whether an observed difference between arms is compatible with chance variation.

What would an inferential comparison add?

In general, a comparison of two group means estimates a contrast between the groups and quantifies uncertainty around that estimate. A confidence interval gives a range of values compatible with the data and the assumptions of the analysis, at the stated confidence level. A test can also produce a p-value, which describes how unusual the data would be under a specified null hypothesis and model. Neither a p-value nor a confidence interval establishes clinical importance on its own. The registry record does not report either kind of inferential result for this primary endpoint.

The record explicitly indicates that values were missing or not estimable for a two-arm comparison of the continuous endpoint. It is therefore important not to fill in a test, interval, or treatment contrast from the arm summaries. The registry’s stated reason means a comparative result is unavailable in the posted record. It does not mean that the groups are equivalent, nor does it establish that a difference exists.

Why does variability matter?

In general, greater variability makes a group mean less precisely estimated when other factors are held constant. The standard deviations reported for this endpoint are 6.3 in the cycloserine arm and 12.7 in the placebo arm. The larger spread in the placebo summary signals more dispersion in that group’s observations. A standard deviation is not the standard error, however, and it is not a direct measure of how precisely the between-group contrast is estimated.

Some continuous outcomes can be skewed or contain observations that are far from the group average. In general, such features can affect how well a normal-based analysis represents the data. The record does not report the individual outcome distributions, model diagnostics, or whether an alternative method was considered. The fact that a planning illustration is described as using a normal approximation does not establish that a particular inferential model was used for the trial’s endpoint.

What does the design record establish?

The registry records randomized allocation, triple masking, and a factorial model. Its brief summary describes a double-blind, between-groups study. Randomization is intended, in general, to reduce systematic differences between assigned groups, while masking can reduce some forms of bias. The record does not explain the factorial factors or the allocation structure, and it does not state who was masked. It is not possible to infer those missing design details from the labels alone.

The endpoint is reported for participants described as completing the 4-week follow-up, and the two arm summaries each have n=8.0. In general, restricting an analysis to follow-up completers can affect how well results represent all randomized participants if completion is related to outcome or treatment assignment. The record does not say whether the analysis followed an intention-to-treat principle, how missing observations were handled, or whether the endpoint was analyzed using another population definition.

What do planning assumptions mean?

The registry describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the trial had a particular probability of detecting an effect. No sample-size result for this endpoint is available because the registry identifies the two-arm comparison as missing or not estimable. The record does not report the trial’s own sample-size justification or a statistical analysis plan.

Overall, the available endpoint information supports a descriptive reading of the group means and standard deviations. It does not support a numerical estimate of an adjusted or unadjusted treatment contrast, a claim of statistical significance, or a judgment about the endpoint’s precision based on a confidence interval.

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("Cycloserine", "Placebo")
n   <- c(8, 8)
m   <- c(10.3, 13.9)
sp  <- c(6.3, 12.7)
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  Cycloserine  8  10.300  6.300  5.033  15.567
CARM  Placebo  8  13.900  12.700  3.283  24.517

11. Multiplicity, Missing Data and Analysis Populations

The registry summary describes several aims and measures: smoking cue reactivity, smoking behavior, memory performance, and safety and tolerability. The registry lists Cigarettes Smoked Per Day as the primary outcome and urinary cotinine as a secondary outcome. It reports two secondary outcomes and three outcome measures. When a study evaluates multiple outcomes or comparisons, the chance of at least one false-positive finding can increase if many tests are conducted. In general, prespecified outcome priorities and multiplicity procedures help readers interpret a set of results. A multiplicity strategy is not reported in the registry record.

The registry records zero posted analyses. For the primary continuous endpoint, it specifically states that values are missing or not estimable for a two-arm comparison. Therefore there is no reported inferential result to assess for multiplicity adjustment or to compare with a prespecified analysis plan. The record does not report which outcomes were included in any final analysis, whether outcomes or timepoints were selected after examining data, or whether a correction for multiple testing was used.

The endpoint description defines the analysis population as participants who completed the 4-week follow-up timepoint. The reported arm sample sizes are n=8.0 each. The record does not provide a participant-flow account, the amount or reasons for missing endpoint data, or a missing-data method such as imputation or a sensitivity analysis. It also does not specify whether all randomized participants were included in any analysis. Thus, the displayed summaries should not be assumed to represent an intention-to-treat analysis.

These omissions limit assessment of selection and missing-data bias. In general, a completer analysis can be difficult to interpret if follow-up completion is associated with smoking behavior or group assignment. The registry record does not provide information to determine whether that concern applies in this study.

12. Safety Results

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

Other (non-serious) adverse events

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

The adverse-event record lists 12 participants at risk in the cycloserine group and 13 in the placebo group for serious adverse events. It records zero serious adverse events in each group. It also lists 12 and 13 participants at risk, respectively, for other adverse events, with zero other adverse events recorded in each group. The record does not list serious adverse-event terms.

These figures describe the registry’s posted event counts and at-risk groups. They are not a guarantee that an event could not occur, and they do not establish that the treatments have identical safety profiles. In general, zero recorded events in a study does not rule out uncommon events, particularly when the amount of safety information is limited. The registry does not provide further detail about event collection, observation time for safety, or whether all events were actively solicited.

Deaths are not reported in the registry record. The adverse-event group sizes differ from the reported primary-outcome sample sizes, and the record does not explain the relationship between these populations. These safety counts should be interpreted separately from the cigarettes-per-day endpoint.

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

The posted primary-outcome data describe cigarettes smoked per day at the 1 week follow-up among the participants included in the registry’s stated analysis population. The cycloserine group mean was 10.3, with a standard deviation of 6.3 and n=8.0. The placebo group mean was 13.9, with a standard deviation of 12.7 and n=8.0. The cycloserine group’s mean is numerically lower in these descriptive summaries.

That observation is not an inferential conclusion. The registry does not report a between-group estimate, confidence interval, or p-value, and it notes that values were missing or not estimable for a two-arm comparison of this continuous outcome. The summaries therefore do not show whether the observed group pattern is distinguishable from random variation, or how precisely a treatment contrast could be estimated. They also do not establish that the groups are equivalent.

The endpoint is one component of a broader study described as examining cue reactivity, smoking behavior, memory performance, and safety and tolerability. The primary endpoint summaries cannot answer those other questions. The record’s brief summary describes measurements of smoking urges and physiological responses to cues, as well as memory tasks and cotinine. Results for those aims are not included in the primary-outcome summaries.

The registry reports enrollment as 20 but gives an analyzed endpoint sample size of n=8.0 in each arm. Its endpoint description identifies 4-week follow-up completers as the analysis population, while the endpoint timeframe is 1 week. Without participant flow or a fuller account of the analysis population, it is not possible to determine how representative the reported means are of all randomized participants.

In general, a treatment effect is judged using the estimated contrast, its uncertainty, the outcome’s relevance, and the study’s design and limitations. The registry record does not provide enough comparative statistical information to make that assessment for this endpoint. The posted data support a description of the arm summaries, not medical advice or a claim that cycloserine does or does not change smoking behavior.

14. Why This Trial Matters Statistically

This record illustrates a distinction that is central to clinical statistics: descriptive arm summaries are not the same as a comparative treatment estimate. Means and standard deviations can show the observed group patterns and variation, but they do not indicate how uncertain the difference between groups is. Without a reported contrast and uncertainty measure, readers cannot assess statistical precision from the registry’s endpoint results.

The endpoint also highlights the importance of defining the analysis population and follow-up time clearly. The primary measure is specified at the 1 week follow-up, while the endpoint description identifies participants who completed the 4-week follow-up as the analysis population. The record does not explain how those definitions relate or provide participant flow. In general, knowing which participants contributed data and how missing observations were handled is essential for evaluating the potential for bias.

The study record lists a factorial model and triple masking, while the brief summary describes a double-blind, between-groups study. These labels are meaningful design information, but the missing details about the factorial structure and masking roles limit how specifically the design can be evaluated. This is a reminder that structured registry labels do not replace an explanation of the design and analysis.

Finally, the registry identifies no estimable two-arm comparison for the continuous primary endpoint. This is not a null finding and should not be read as evidence of no effect. It is an absence of a posted comparative result. Distinguishing unavailable analysis from a well-estimated result near no difference is important when interpreting clinical trial evidence.

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 main limitation for interpreting the primary outcome is that the registry posts arm-level descriptive summaries but no comparative analysis. It identifies the two-arm comparison as missing or not estimable. There is consequently no reported treatment contrast, confidence interval, or p-value for cigarettes smoked per day.

The endpoint description defines the analysis population as participants who completed the 4-week follow-up, and each arm’s reported sample size is n=8.0. The registry reports enrollment as 20 but does not provide a participant-flow account explaining the relationship between enrollment and the endpoint sample sizes. It also does not report the extent or reasons for missing outcome data, or describe a missing-data method. The timeframe of the endpoint is 1 week, and the connection to the 4-week completion criterion is not explained.

The record does not provide individual-level data, distributions, model diagnostics, or details about the measurement and recall procedure for cigarettes smoked per day. It does not report the factorial factors or how they were incorporated into an analysis. Although masking is recorded as triple, the masked roles are not specified; the brief summary instead uses the description double-blind. The record does not resolve that difference in terminology.

The registry describes multiple study aims and outcomes, but does not report a statistical analysis plan or a multiplicity procedure. No posted analyses are listed. The available information is therefore insufficient to evaluate whether outcome selection, missing data, or analytic choices affected the primary result. These limitations constrain interpretation of the descriptive summaries and prevent a firm assessment of comparative effect or precision.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The Effect of Cycloserine on Smoking Behavior in Nicotine Dependent Smokers — NCT00633256.
• Registry record last updated 2012-04-11; status last verified 2012-03.
• Results first posted 2012-04-11.
• 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 study of cycloserine versus matched placebo in nicotine-dependent smokers, with smoking cue exposure. The study is listed as triple-masked and factorial; its summary describes a double-blind, between-groups design. Enrollment is recorded as 20.

The primary outcome is cigarettes smoked per day at the 1 week follow-up, with the analysis population described as participants who completed the 4-week follow-up. The cycloserine arm mean was 10.3 with standard deviation 6.3 and n=8.0; the placebo arm mean was 13.9 with standard deviation 12.7 and n=8.0. The registry does not report a comparative analysis and states that values were missing or not estimable for a two-arm continuous-outcome comparison.

The record also describes aims concerning cue reactivity, smoking behavior, memory, and safety, and lists urinary cotinine as a secondary outcome. It does not report a statistical analysis plan, missing-data approach, or multiplicity procedure. The adverse-event record lists zero serious and zero other adverse events in both groups; deaths are not reported in the registry record.