This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study of Lunesta Versus Placebo for Sleep Problems Related to Smoking Cessation and Zyban (NCT00511134), a randomized phase 4 study. The primary outcome is Level of Insomnia as Measured by the Insomnia Severity Index.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00511134 |
| Phase | Phase 4 |
| Condition | Insomnia, Nicotine Dependence |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 4 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Yale University |
| Results posted | Yes |
2. Clinical Question
The trial asked whether eszopiclone, taken alongside bupropion during a smoking-cessation attempt, would be associated with fewer sleep problems than placebo alongside bupropion. The primary outcome was the Insomnia Severity Index (ISI), assessed 6 weeks after the target smoking quit date. The registry description also names difficulty falling asleep, difficulty staying asleep, sleep quality, and insomnia-related fatigue and distress as areas of interest.
Population
Healthy smokers attempting smoking cessation, with insomnia and nicotine dependence listed as conditions. The record says baseline descriptive data were examined for 4 participants, while outcome measures were available for 2.
Intervention
Zyban (bupropion) plus Lunesta (eszopiclone). The planned regimen was Zyban 150 mg qd for 7 days, then 150 mg bid for 6 weeks, plus Lunesta 3 mg qd for 6 weeks.
Comparator
Zyban plus matched placebo. The planned Zyban regimen was the same as in the eszopiclone arm; placebo was described as 1 pill per day for 6 weeks.
Primary question
What level of insomnia was recorded on the ISI 6 weeks after the target quit date in each group, and could the available data support a statistical comparison?
The registry lists smoking abstinence, measured by self-reported smoking and confirmed by carbon monoxide level, as a secondary outcome. The posted information does not establish a reliable between-group effect. The very limited outcome availability and the registry’s statement that comparisons were not possible are central to interpreting the result.
3. Trial Design
This was a randomized, triple-masked, parallel-group Phase 4 study sponsored by Yale University. It enrolled 4 participants and is listed as terminated. The registry gives a start date of 2007-04 and a primary completion date of 2008-12; it does not report why the study was terminated.
The planned study duration was 7 weeks. Participants were to begin Zyban at the start of week 1 and attempt to quit smoking at the start of week 2. Lunesta or matched placebo was to begin on the target quit date and continue for 6 weeks. All participants were also to receive eight weekly sessions of brief individual supportive smoking-cessation counseling. These are the planned procedures described in the registry; the record does not establish how fully they were completed.
The two planned groups were Zyban plus Lunesta and Zyban plus placebo. The registry reports one participant in each group for the primary outcome, with ISI values of 11 and 5, respectively. The registry also states that outcome measures were available for 2 participants, despite baseline descriptive data being examined for 4. It does not explain the difference between enrollment and outcome availability.
Randomization and masking describe intended protections against allocation and assessment bias, but they do not overcome the limitations of sparse outcome data. Details such as the randomization sequence, concealment procedures, masking assessment, and statistical analysis plan are not reported in the registry record. The record also does not explain the termination or describe whether enrollment, treatment, follow-up, or analysis ended early.
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: Major reasons for exclusion at phone screen were report of no sleep problems, use of illegal substances, psychiatric or medical exclusions, and low smoking. Major reasons for exclusion during the in-person screening process included withdrawal of informed consent, alcohol or illicit drug use, and low smoking.
Overall Study
| Stage | Zyban + Lunesta | Zyban + Placebo |
|---|---|---|
| STARTED | 1 | 3 |
| COMPLETED | 1 | 1 |
| NOT COMPLETED | 0 | 2 |
Reasons for not completing this period:
| Reason | Zyban + Lunesta | Zyban + Placebo |
|---|---|---|
| Withdrawal by Subject | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: Baseline descriptive data was examined for the 4 participants. Outcome measures were available for 2 participants. Due to the small number of participants, statistical comparisons were not able to be performed.
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.
| Characteristic | Unit | Zyban + Lunesta | Zyban + Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 1 | 3 | 4 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 3 | 4 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 0 | 1 | 1 |
| Sex: Female, Male: Male | Participants | 1 | 2 | 3 |
| Region of Enrollment: United States | participants | 1 | 3 | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Level of Insomnia as Measured by the Insomnia Severity Index, measured over 6 weeks after target smoking quit date.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | Units on a Scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the level of insomnia measured by the Insomnia Severity Index 6 weeks after the target smoking quit date. The ISI is described as a 13-item self-report measure covering insomnia symptoms, consequences, and subjective distress related to sleep problems. Participants rate symptoms and consequences on a 5-point Likert scale. The first 7 items are summed to create a total insomnia score ranging from 0-28.
The measure is relevant to the trial question because it captures reported insomnia and its perceived consequences, rather than relying only on a single sleep symptom. A total score can provide a structured way to describe the overall level of insomnia at the stated follow-up. However, the registry identifies the outcome parameter as the median and its dispersion as the full range. With one participant reported in each group, the observed group values are individual observations; they cannot characterize the spread of outcomes within either group.
The posted ISI value was 11 in the Zyban plus Lunesta group and 5 in the Zyban plus placebo group. These values describe the participants with reported outcomes, not a stable estimate of what would generally occur in either treatment group. The registry does not report a formal between-group comparison that can be interpreted alongside these values.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome is descriptive. For the participant with an outcome in the Zyban plus Lunesta group, the ISI value was 11; for the participant with an outcome in the Zyban plus placebo group, it was 5. The registry reports a median and full range for the endpoint, but with one observed value in each group, each reported range contains only that participant’s value. These observations do not establish the typical outcome for either group or the size of a dependable treatment contrast.
The registry explicitly states that outcome measures were available for 2 participants and that statistical comparisons could not be performed because of the small number of participants. That limitation is appropriate to emphasize. The observed values can be reported as individual data, but they do not support a reliable conclusion about whether the groups differ in insomnia outcomes. No confidence interval or interpretable estimate of uncertainty for a group contrast is reported.
There is also an inconsistency within the posted analysis information: the narrative says statistical comparisons were not possible, while the reported-analysis entry gives a p-value of <0.05 alongside the method description “Descriptive data.” No test statistic, inferential method, or corresponding estimate is reported. The p-value therefore cannot be reconciled with the narrative or interpreted as evidence from a specified statistical comparison. It should not replace the registry’s explicit statement that comparisons could not be performed.
The study is listed as terminated, and outcome data were available for only part of the enrolled group. The reasons for termination and for unavailable outcomes are not reported in the registry record. Without those details, it is not possible to determine whether missing outcomes were related to participants’ experiences, treatment assignment, or other circumstances. That uncertainty further limits interpretation.
The secondary outcome concerns smoking abstinence assessed by self-report and confirmed by carbon monoxide level. The registry lists that outcome but does not report its results in the information available for interpretation. No conclusion about abstinence can be drawn from the primary ISI values.
Overall, the record documents two individual ISI observations and a design intended to compare eszopiclone with placebo on a bupropion background. It does not provide an interpretable statistical comparison or sufficient outcome data to characterize group-level effects. The estimates are too sparse to distinguish a treatment-related pattern from ordinary participant-to-participant variation.
9. Statistical Methods Explained
Descriptive statistics and individual observations
The registry identifies the primary outcome statistic as a median and the accompanying spread as the full range. In general, a median describes the central position of ordered observations, while a range gives the lowest and highest observed values. These summaries can be useful for skewed data or small samples, but they depend on having enough observations to describe a group. In this trial, the registry reports one outcome observation in each group, so the median is simply that participant’s observed value and the range does not describe variation across participants.
The posted values are 11 for Zyban plus Lunesta and 5 for Zyban plus placebo. They should be read as descriptions of the two participants with outcome data. The difference between these observations is not, by itself, an estimate that can be generalized to the target population. The record does not report a model or procedure that adjusts for participant characteristics, baseline ISI, or other factors.
What can a p-value say?
In general, a p-value is calculated under a specified statistical model and a null hypothesis. Its interpretation depends on the analysis, the assumptions, and the data used. A p-value does not measure the size or clinical importance of an effect, and it does not provide the probability that the null hypothesis is true. A reported p-value is most informative when accompanied by a clearly described method and an effect estimate with an uncertainty interval.
For this record, the analysis entry states p <0.05 but labels the method “Descriptive data.” The primary-outcome description separately says statistical comparisons were not able to be performed. The entry does not include a test statistic, analysis method, or effect estimate, so the p-value cannot be interpreted as a defined comparison between the two groups. It does not resolve the limitations created by the sparse outcome data.
Why confidence intervals matter
In general, a confidence interval expresses the uncertainty around an estimate under the assumptions of the method used to construct it. A narrow interval indicates greater precision than a wide interval, although the interpretation depends on the study design and analysis. An interval does not repair bias or missing data, and it cannot make an unreported or unsuitable comparison valid.
No interval bounds for a between-group primary-outcome estimate are reported in the registry record. The analysis entry includes a 95% confidence-level designation but does not provide lower or upper bounds. Without an estimate and interval, readers cannot assess the precision of a group contrast from the reported analysis.
What the planning illustration represents
The registry’s sample-size assumptions describe a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. The illustration varies the effect to detect as a stated fraction of the observed effect. For time-to-event outcomes, the stated convention is a total event count; for other outcomes, it is participants per arm.
These assumptions describe a planning exercise, not the design rationale for this trial. The registry does not report its own sample-size justification, and no numerical planning results are available in the record. Any planning illustration based on an observed effect from this very small set of outcomes is not observed power and should not be treated as evidence that the study was adequately sized. A planning calculation cannot create additional observed information or compensate for outcome data being available for only 2 participants.
Why over-dispersion and model choice are general concerns
General statistical methods often make assumptions about how outcomes vary across participants. Over-dispersion means that observed variation is greater than a model expects; when present and ignored, uncertainty can be understated. Model choice also needs to match the outcome scale, design, and data structure. These are general considerations, not reported features of this analysis. The registry does not describe a fitted model, an over-dispersion assessment, or a model-based primary comparison.
What randomization and masking can and cannot do
In general, randomization aims to make treatment groups comparable on average, while masking can reduce bias in treatment delivery, participant reporting, and outcome assessment. These design features do not guarantee balance in a particular small trial, nor can they address outcomes that are not observed. The registry records randomized allocation, triple masking, and a parallel model, but methodological details of implementation are not reported. With the small number of reported outcome observations, the design labels alone cannot establish that observed score differences reflect treatment assignment.
The registry does not report an analysis plan, interim analyses, a multiplicity strategy, or details of the analysis population. These omissions mean that the reported p-value cannot be placed in a clear prespecified inferential framework. The most defensible statistical reading is therefore descriptive: two individual outcome values are posted, and the record says a formal comparison was not possible.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Descriptive data | not reported | < 0.050 |
The registry’s primary-outcome narrative says statistical comparisons could not be performed because of the small number of participants. The reported-analysis entry, however, labels the analysis “Descriptive data” and gives p <0.05. It does not identify a test, provide a test statistic, or report a between-group estimate and confidence interval. The two statements do not form a coherent, fully documented inferential analysis.
The arm-level summaries report one ISI value in each group: 11 with Zyban plus Lunesta and 5 with Zyban plus placebo. Those are descriptive observations. No separate recalculated inferential result is reported in the registry record, and the arm summaries do not provide enough information to interpret the reported p-value as a specified statistical comparison. The reported p-value should therefore be presented as an entry in the record, not as a supported finding of a group difference.
The record does not indicate a discrepancy between a sponsor analysis and a recalculation. The clearest interpretation rests on the limitations stated in the registry itself: outcome data were available for 2 participants, and comparisons could not be performed. The descriptive scores do not overturn that limitation.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists the ISI as the primary outcome and smoking abstinence, measured by self-report and confirmed by carbon monoxide level, as a secondary outcome. It also describes several symptom domains in the study hypothesis, including falling asleep, staying asleep, sleep quality, fatigue, and distress. The record does not report a multiplicity strategy for handling several outcomes or symptom domains. Without such information, it is not possible to determine whether any reported statistical result was adjusted for multiple comparisons or how the analyses were prioritized.
Outcome measures were available for 2 participants, while baseline descriptive data were examined for 4 participants. The record does not explain why outcome data were unavailable for some participants, whether missingness differed by group, or how missing outcomes were handled. It does not report imputation or another method for addressing missing data. Consequently, the reported outcome values describe participants with available measurements; the record does not establish how representative they are of all enrolled participants.
The arm summaries list one participant in each group for the primary outcome. The record does not specify a detailed analysis population, such as whether the primary analysis was intended to include all randomized participants or only those with observed outcomes. It also does not report adherence, withdrawals, or exclusions by arm. Those details matter because an analysis restricted to participants with measurements can be affected if outcome availability is related to treatment or outcome.
The termination status and the disparity between enrollment and outcome availability add context, but the reasons for either are not reported in the registry record. There is no basis for attributing missingness to a particular cause or for assuming that it was unrelated to the outcome. These limitations, along with the absence of a reported multiplicity plan, constrain any inferential interpretation.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Zyban + Lunesta | 0 | 1 | 0.0% |
| Zyban + Placebo | 0 | 3 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Zyban + Lunesta | 0 of 1 |
| Zyban + Placebo | 0 of 3 |
The adverse-event record lists no serious adverse events among the participants at risk in either group. It also lists no other adverse events among those at risk. The figures are reported as 1 participant at risk in the Zyban plus Lunesta group and 3 in the Zyban plus placebo group. These safety denominators differ from the primary-outcome arm summaries, which list one participant in each group; the registry does not explain the difference.
The death fields are not populated, and the record does not report serious adverse-event terms. Accordingly, the posted figures support only a narrow description of the recorded counts. They do not establish that no events occurred outside the reporting captured in the record, nor do they establish comparable safety between groups. With the small and differing at-risk counts, absence of recorded events is not a precise estimate of event risk.
The registry does not provide further details about event collection, follow-up completeness, or the handling of missing safety information. These figures should be read as registry-recorded adverse-event data, not as a comprehensive assessment of the safety of either regimen.
13. What the Result Does, and Does Not, Mean
The record shows that a randomized, triple-masked trial was intended to compare eszopiclone with placebo for insomnia during bupropion-assisted smoking cessation. It reports ISI values of 11 and 5 for the two participants with primary-outcome data. The registry says outcome measures were available for 2 participants and that statistical comparisons could not be performed.
Those observations do not establish whether eszopiclone changed insomnia outcomes relative to placebo. A value in each group provides little information about the distribution of outcomes among the intended study population, and the record does not give a valid, fully described inferential comparison. The p-value entry of <0.05 is not accompanied by a stated test or estimate and conflicts with the narrative statement that comparison was not possible.
The record also does not report results for the listed smoking-abstinence outcome. It therefore does not support conclusions about abstinence. The adverse-event counts record no events among the reported participants at risk, but they are too limited to establish comparative safety.
More broadly, the study’s termination, limited outcome availability, and lack of reported explanations for missing data restrict what can be learned. The results are best treated as a small set of descriptive observations, not as a reliable estimate of treatment effect or evidence for a clinical decision. The registry record does not report the reasons for termination, a sample-size justification, or a detailed statistical plan.
14. Why This Trial Matters Statistically
This trial is statistically instructive because its design labels and its available information point in different directions. Randomization and triple masking are important design features, but the primary outcome was available for only 2 participants. When so few outcomes are observed, the central challenge is not choosing a more elaborate model; it is the lack of information for estimating group-level patterns and uncertainty.
The registry also illustrates why a p-value should not be read in isolation. A value of p <0.05 appears in the reported-analysis entry, while the primary-outcome description says a comparison could not be performed. Without the test method, test statistic, estimate, or confidence interval, the p-value cannot be placed in a transparent analysis. The internal tension in the record is itself important for statistical interpretation.
Missing outcomes and termination also matter. The registry gives no explanation for why outcome measures were unavailable for some enrolled participants or why the study was terminated. Those omissions prevent readers from assessing how the observed participants relate to the full enrolled group. The listed secondary outcome has no results in the record, further limiting the available evidence.
The example underscores that planning illustrations and study design features cannot substitute for observed outcomes. A calculation based on a very sparse observed effect cannot turn descriptive data into a precise comparison. Clear reporting of participant flow, analysis populations, prespecified outcomes, methods, and uncertainty is especially valuable when a study ends with limited data.
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.
Important limitations specific to this trial include the small enrollment of 4 participants and primary-outcome data for only 2. The arm summaries report one outcome observation per group, which cannot characterize within-group variability or support a dependable estimate of a population-level contrast. The registry itself says that statistical comparisons could not be performed.
The record does not explain why the study was terminated, why outcome measures were unavailable for some participants, or whether missingness differed between groups. It does not report participant flow, withdrawals, adherence, or exclusions by arm. As a result, the relationship between enrollment, treatment exposure, follow-up, and the posted outcomes remains unclear.
The reported-analysis entry gives p <0.05 but does not describe an inferential method, while the outcome narrative says comparisons could not be performed. No effect estimate or confidence interval bounds are reported. This prevents a coherent assessment of the size and precision of a group contrast.
The registry lists smoking abstinence as a secondary outcome but does not report its results. It also does not report a multiplicity strategy, a detailed statistical plan, a sample-size justification, or interim analyses. The safety denominators differ from the primary-outcome group counts, with no explanation, and event reporting is sparse. These limitations prevent firm conclusions about efficacy, abstinence, or comparative safety from the posted record.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Study of Lunesta Versus Placebo for Sleep Problems Related to Smoking Cessation and Zyban — NCT00511134.
- Registry record last updated 2022-05-09; status last verified 2022-05.
- Results first posted 2009-12-04.
- 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.
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19. Record Summary
This Phase 4 randomized, triple-masked, parallel-group study compared Zyban plus Lunesta with Zyban plus placebo for insomnia during smoking cessation. The registry lists enrollment of 4 and a terminated status. The planned primary outcome was the ISI 6 weeks after the target quit date.
Outcome data were available for 2 participants. The posted ISI values were 11 for Zyban plus Lunesta and 5 for Zyban plus placebo. The registry states that statistical comparisons could not be performed, although a reported-analysis entry gives p <0.05 without a stated inferential method. The record lists smoking abstinence as a secondary outcome but does not report its results. It records no serious or other adverse events among the listed participants at risk, while the reasons for termination and missing outcomes are not reported.