Nicotine Receptor Density & Response to Nicotine Patch: Pt 2 Extended Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nicotine Receptor Density & Response to Nicotine Patch: Pt 2 Extended Treatment (NCT02676375), a randomized phase 4 study. The primary outcome is Exhaled Carbon Monoxide (CO) as Parts Per Million (PPM).

2. Clinical Question

3. Trial Design

The registry record describes a randomized, parallel-group Phase 4 trial with no masking. The trial is marked completed. Its stated enrollment is 42. The brief summary, however, describes a plan to enroll 45 participants, with 15 assigned to each of three treatment arms. Those are different figures: the stated enrollment is the record's enrollment value, while the brief summary describes the intended enrollment. The record does not explain the difference or report actual arm-level enrollment at randomization.

The arms were standard monotherapy, combination extended treatment, and combination extended treatment with home visits and calls. The arm descriptions characterize standard monotherapy as usual treatment beginning with one smoking-cessation medication plus group therapy. The extended-treatment arms used multiple standard medications and group therapy, with home visits and calls added to one arm. The brief summary describes weekly group counseling during treatment and a lead-in visit for baseline assessment and eligibility checks. It also gives additional details about the treatment options, but does not state which specific medication each participant received.

The registry record gives a study start of 2014-01 and a primary completion date of 2016-06. The sponsor is Brentwood Biomedical Research Institute. The primary outcome was exhaled carbon monoxide in PPM, recorded as a mean with standard deviation, with the timeframe listed as week 0, week 12, and week 26. Although the record identifies this outcome, it reports zero analyses. No numerical outcome estimates or treatment-group comparisons are included in the posted results.

Random allocation can support comparisons between assigned groups, but the record does not provide details of the randomization procedure beyond describing random assignment. Masking is listed as none. That matters when interpreting outcomes that might be influenced by awareness of treatment, although the primary outcome is an instrument-based measurement. The record does not report whether outcome assessors were masked or how measurements were obtained.

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

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 Exhaled Carbon Monoxide (CO) as Parts Per Million (PPM), measured over Measured week 0, 12, and 26.

The primary endpoint is exhaled carbon monoxide, measured in parts per million. The record describes the measure as a mean with standard deviation and lists measurement times at week 0, week 12, and week 26. Its outcome description says expired carbon monoxide was measured to evaluate smoking abstinence. A value at or below 3 PPM is considered abstinent in the registry record.

Carbon monoxide is used as an objective indicator related to recent smoking, rather than relying only on a participant's account. The threshold gives the measure a clinical interpretation in the study: values at or below it are categorized as consistent with abstinence according to the record. The outcome is still reported as a continuous measure, so group means and their variability would describe the distribution of measured values as well as how far values lie from that threshold. A group mean alone would not reveal how many participants met the abstinence threshold.

The schedule is not fully clear from the wording. The outcome description refers to weekly measurements, while its timeframe names week 0, week 12, and week 26. The registry record does not explain whether the listed weeks are particular assessment visits within a weekly schedule or the complete set of scheduled measurements. Most importantly, it reports no numerical CO results, no proportion meeting the threshold, and no estimates comparing treatment arms. The listed endpoint therefore defines what was assessed, but does not show the observed outcome pattern.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group design, but the statistical analysis details are not reported in the registry record. The record identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. It does not report a model, a test, an adjusted estimate, a confidence interval, or an analysis population. Since the record lists zero analyses, no inferential result for the primary outcome is available to interpret.

What does a mean and standard deviation describe?

General statistical explanation: a mean describes the average measured value in a group. A standard deviation describes how dispersed individual measurements are around that average. These summaries answer different questions: a mean describes the group's central level, while a standard deviation describes variability among observations. A mean and standard deviation do not, on their own, show the number of participants who crossed a clinical or operational threshold. For this trial, the record identifies at or below 3 PPM as the threshold considered abstinent, but provides no group-level CO summaries or counts meeting that threshold.

Because the endpoint is listed at week 0, week 12, and week 26, a complete analysis could describe measurements at each time and compare groups over time. General statistical explanation: repeated measurements from the same participant are related rather than independent. An analysis that uses measurements across time ordinarily needs to account for that within-person association. The registry record does not report whether the analysis used repeated-measures methods, separate time-specific comparisons, or another approach. It also does not clarify whether the outcome description's reference to weekly measurements means measurements beyond the listed time points.

What would a treatment contrast mean?

General statistical explanation: a treatment contrast compares an outcome between assigned groups. For a continuous measure such as CO, a contrast might be expressed as a difference in group means, depending on the chosen analysis. The contrast's direction depends on how groups are ordered and how the outcome is defined. Its estimate describes the observed magnitude, while an uncertainty interval describes the range of values reasonably compatible with the data under the analysis assumptions. A p-value, if reported, addresses compatibility with a specified null hypothesis under those assumptions; it does not describe the size or clinical importance of an effect.

None of those quantities is reported for the primary endpoint in this record. There is no basis for inferring a treatment contrast from the design description, enrollment, or adverse-event counts. Similarly, the abstinence threshold does not permit reconstruction of group means or the number of participants classified as abstinent.

What does randomization contribute?

General statistical explanation: random assignment is designed to reduce systematic differences between treatment groups at the point of assignment. It supports causal comparisons when the analysis preserves the randomized groups and when outcomes are adequately observed. Randomization does not prevent missing measurements, departures from assigned treatment, or chance imbalances. The registry record does not report allocation details, baseline characteristics, adherence, withdrawals, or the population used for analysis. It is therefore not possible to assess those features from the record.

The design is recorded as unmasked. General statistical explanation: when participants and study staff know the assigned treatment, expectations or differences in care can affect behavior and some aspects of outcome collection. An objective measurement can reduce some forms of subjectivity, but does not by itself establish that measurement was free of bias. The registry record does not say whether outcome assessors were masked or describe measurement procedures.

How should planning calculations be read?

General statistical explanation: a sample-size planning illustration asks how much information might be needed to detect a specified effect under stated assumptions. The record describes an illustration based on a fraction of the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such an illustration is not the trial's own design justification, and the registry record does not report a sample-size justification. It is also not observed power. Planning values depend on their assumptions and are not evidence that a treatment effect exists or that a study could reliably detect it.

The record's stated sample-size assumptions do not supply a reported primary-outcome effect estimate or analysis. Any planning illustration should therefore be interpreted as hypothetical rather than as a trial result. The registry record does not report the calculations' numerical output in the information available for this analysis. These planning assumptions also do not clarify the discrepancy between the stated enrollment and the enrollment planned in the brief summary.

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model underestimates variability, its uncertainty estimates can be too narrow. This is a general issue for count outcomes and is not a reported feature of this trial's continuous CO endpoint. The record does not identify an over-dispersed model or provide the data needed to assess distributional assumptions. No model diagnostics or sensitivity analyses are reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is listed at week 0, week 12, and week 26, and the trial has three treatment arms. Considering multiple time points and several possible group contrasts can create multiplicity: the more hypotheses examined, the greater the chance that at least one result appears notable by chance if no adjustment or prioritization is used. General statistical explanation: a prespecified primary contrast and time point can help define the main inferential question; adjustment methods can also address multiple testing. The registry record does not report a multiplicity strategy, a prespecified contrast, or which time point would govern a primary treatment comparison.

The registry record does not report a statistical analysis plan, the handling of missing CO measurements, or the analysis population. It does not say whether the primary analysis was based on assignment, treatment received, or participants with observed measurements. No information is reported about withdrawals, missed assessments, protocol deviations, treatment adherence, or imputation. These omissions limit interpretation because missing observations and the way they are handled can affect estimates and their uncertainty.

The brief summary describes baseline assessment and eligibility checks, but the registry record does not give baseline outcome summaries or explain how baseline CO was incorporated into an analysis. It also does not report whether adjusted or unadjusted comparisons were planned. No interim analyses or stopping rules are reported in the registry record; their presence or absence cannot be inferred from the lack of posted analyses. The registry lists one outcome measure but no analyses. That means multiplicity procedures and missing-data methods cannot be evaluated from numerical results.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event summaries list zero serious adverse events in each treatment arm and zero deaths in each arm. For other adverse events, the record lists 6 affected among 13 at risk for standard monotherapy, 3 among 10 at risk for combination extended treatment, and 3 among 11 at risk for combination extended treatment with home visits and calls. These are the posted group-specific counts; they should be read as separate summaries, not combined into an overall total.

The labels distinguish serious adverse events from other adverse events. A zero serious-event count means none were recorded in the listed group summary; it does not establish that no unrecorded event occurred, or that the strategies have identical safety profiles. The registry record does not provide the types of other adverse events, their severity, timing, duration, or whether an event was considered related to treatment. It also does not explain the different at-risk counts or define the safety observation period in the information.

These safety counts are descriptive and do not provide a comparative statistical analysis. The record reports no confidence intervals or formal tests for adverse events. The counts at risk should not be assumed to be the randomized group sizes, and the brief summary's planned group counts should not be substituted for them. The summaries therefore describe recorded events in the stated safety groups, with limited information about event definitions and follow-up.

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

The registry record establishes that a randomized, parallel-group study compared standard monotherapy with two extended combination-treatment strategies among treatment-seeking cigarette smokers with schizophrenia. It identifies exhaled carbon monoxide as the primary outcome and defines at or below 3 PPM as an abstinence threshold. It also reports adverse-event counts for each treatment arm. These details describe the study question and some recorded safety information.

The posted results do not establish whether one treatment strategy produced lower mean CO, whether CO changed over time, or whether the groups differed in abstinence. No numerical primary-outcome results, treatment contrasts, confidence intervals, or p-values are reported. The record's zero analyses means there is no reported inferential analysis to evaluate. This absence should not be read as a finding of no difference; it leaves the treatment comparison unquantified.

The threshold cannot be used to infer how many participants were abstinent because no individual measurements or threshold counts are reported. Likewise, the safety counts do not show comparative risk with statistical precision, and they do not describe event types or treatment attribution. Zero serious adverse events and zero deaths are the values recorded in the arm summaries, but those values do not establish broad safety or equivalence.

The stated enrollment and planned enrollment in the brief summary differ, and the record does not explain why. The safety group counts are not a substitute for a report of randomized arm sizes or a participant flow account. Without information on missing observations, analysis populations, treatment exposure, and outcome estimates, readers cannot assess how closely the posted summaries represent all randomized participants or how robust a treatment comparison would be.

In short, the registry record supports a description of the design, endpoint, and posted adverse-event summaries. It does not support a conclusion about the size, direction, precision, or clinical importance of a primary treatment effect. Any such conclusion would require outcome analyses and details not reported in the registry record.

13. Why This Trial Matters Statistically

This trial raises statistical questions that are important when a study includes multiple treatment strategies and repeated outcome assessments. The primary endpoint is a continuous CO measure, but its interpretation also involves a specified abstinence threshold. Those are related but distinct summaries: the continuous outcome describes measured levels, while threshold-based classification describes whether a measurement falls within the study's abstinence definition. Reporting both can help readers understand different aspects of an outcome, but the registry record provides no numerical results for either.

The three-arm design includes a standard-treatment comparator and two versions of extended combination treatment, one with home visits and calls. A clear statistical analysis plan would specify which group contrasts and assessment times address the primary question, and how multiplicity is handled. The registry record does not report those details. Without them, the intended hierarchy among potential comparisons cannot be assessed.

The study is marked randomized and unmasked. That combination highlights the value of understanding allocation, outcome collection, and analysis populations. Randomization can support fair comparisons, while unmasked assignment and missing outcomes may still matter. The record does not report enough information to assess these issues or the precision of a treatment estimate. It reports the endpoint and design, but not the analyses needed to connect them.

The difference between stated enrollment and the enrollment described in the brief summary also illustrates why planned recruitment and recorded enrollment should be distinguished. The record does not reconcile the figures. The adverse-event summaries use their own at-risk counts, which likewise should not be mistaken for planned enrollment or randomized group totals. Clear participant-flow and analysis-population information would help readers understand how these counts relate.

Statistically, the central lesson is that a registered outcome and a completed trial do not by themselves provide evidence about the magnitude or uncertainty of a treatment effect. Outcome estimates, uncertainty intervals, analysis methods, and information about missing data are needed for that interpretation. Their absence in this record leaves a descriptive account of the study rather than a quantitative answer to its primary comparison.

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 limitations of interpretation arise from what is not reported in the registry record. The primary endpoint is named and its measurement times are listed, but there are no numerical results for mean CO or standard deviation and no analysis comparing arms. The record therefore cannot show the degree of separation between groups, the variability of the measurements, or the precision of any treatment contrast.

The outcome description refers to weekly measurements, while the timeframe lists week 0, week 12, and week 26. The registry record does not clarify the assessment schedule. It also does not provide a threshold-based abstinence count, even though it defines at or below 3 PPM as considered abstinent. The mean outcome and threshold classification therefore cannot be considered together from the reported information.

The record gives an enrollment of 42 and a brief-summary plan to enroll 45, with 15 per treatment arm. It does not explain the difference, report the final randomized count by arm, or provide participant flow. The arm-specific numbers at risk in the adverse-event summaries cannot resolve this because the record does not describe how those safety populations were defined or why their counts differ.

Further limitations include the absence of a reported statistical analysis plan, randomization details, baseline characteristics, missing-data methods, analysis-population definitions, treatment adherence information, and information about withdrawals. The registry record also does not report whether CO assessors were masked, or describe outcome measurement procedures. These gaps prevent evaluation of the analysis choices and the extent to which the observed groups and reported safety summaries reflect the randomized comparison.

Finally, the record reports zero analyses. No formal primary-outcome inference, multiplicity approach, or sensitivity analysis can be assessed. The adverse-event summaries are counts without reported uncertainty estimates or event descriptions. These limitations concern the available registry information; they do not establish that the unreported methods or results were absent from other study materials.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Nicotine Receptor Density & Response to Nicotine Patch: Pt 2 Extended Treatment — NCT02676375.
• Registry record last updated 2019-07-30; status last verified 2019-07.
• Results first posted 2019-07-30.
• 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

NCT02676375 is a completed, randomized, unmasked, parallel-group Phase 4 trial sponsored by Brentwood Biomedical Research Institute. It studied smoking-cessation strategies among treatment-seeking cigarette smokers with schizophrenia. The record describes standard monotherapy, extended combination treatment, and extended combination treatment with home visits and calls. Stated enrollment is 42; the brief summary describes a plan for 45 participants, with 15 per arm. The record does not explain the difference.

The primary outcome was mean exhaled carbon monoxide in PPM, with measurements listed at week 0, week 12, and week 26. The record defines at or below 3 PPM as considered abstinent. It reports one outcome measure and zero analyses, so no numerical primary-outcome comparison is available. Safety summaries list zero serious adverse events and zero deaths in each arm, alongside counts for other adverse events. The record does not report a statistical analysis plan, missing-data methods, or further detail about the adverse events.