Smoking While on Transdermal Nicotine Replacement Therapy: Effects on Craving and Cessation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Smoking While on Transdermal Nicotine Replacement Therapy: Effects on Craving and Cessation (NCT00289653), a na na study. The primary outcome is Carbon Monoxide Levels.

2. Clinical Question

The study description focuses on smoking while using nicotine patches and on changes in expired carbon monoxide and daily cigarette consumption. The brief summary states the expected direction of change, but that statement is not an observed result. The registry record identifies smoking cessation as a secondary outcome, without reporting a cessation result.

Because this was a single-group study, the central question that can be described from the registry is how the recorded outcomes were intended to be assessed during treatment, not how the treatment compared with an untreated or alternative-treatment group. Without a control group, changes over time cannot by themselves distinguish treatment effects from other explanations. The registry record does not report a statistical comparison or an estimate of change.

3. Trial Design

This completed study enrolled 23 participants and used a single open-label treatment arm. The registry lists the allocation as NA and the masking as none. The record lists the sponsor as the Centre for Addiction and Mental Health. The study began in 2005-09, and primary completion was 2006-12.

Participants were adult smokers willing to quit. The arm description says they received escalating doses of transdermal nicotine patch (Nicoderm) over a 9-week treatment period. Brief counselling was included if participants continued to smoke. The registry does not describe the dose schedule, counselling content, visit schedule, or adherence assessment in further detail; those details are not reported in the registry record.

The primary outcome was expired carbon monoxide at week 10. Smoking cessation was listed as a secondary outcome, and the record indicates two outcome measures. It does not report the second measure's title or results in the registry record for this analysis. The registry lists zero analyses. It does not report an analysis population, a statistical analysis plan, or a sample-size justification.

The study is not a randomized comparison. A single treatment arm can describe outcomes among enrolled participants, but without a concurrent control group it cannot establish whether an observed change was caused by the treatment. Open-label status also means masking was absent. The registry record does not report whether outcome assessment was masked or whether any procedures were used to limit bias.

Sample-size illustrations associated with the record are planning exercises based on an observed effect, using two-sided significance level 0.05, equal allocation between two hypothetical arms, and a normal approximation. These are not the study's design: it had one treatment arm. They are not observed power, and the registry record does not report that these assumptions informed the trial's original planning.

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 Carbon Monoxide Levels, measured over measured at week 10.

The primary endpoint was expired carbon monoxide, measured at week 10 and expressed in parts per million. The registry description says the measurement was used to confirm smoking status. Expired carbon monoxide is an objective measure recorded from exhaled breath; in general, an objective measure can complement self-reported smoking information. The registry record does not describe the device, measurement protocol, timing within the visit, or threshold used to classify smoking status.

The outcome is specified as a mean with standard deviation. In general, a mean describes the average measurement in a group, while the standard deviation describes how spread out individual measurements are around that average. These summaries would help characterize the week 10 measurements, but the registry record does not report the mean, standard deviation, or number of participants with a recorded endpoint.

The outcome's stated purpose is confirmation of smoking status, not a direct measure of long-term cessation. Smoking cessation was listed separately as a secondary outcome. The registry record does not report its definition, assessment window, or result. No conclusion about the endpoint's observed level or its relationship to cessation can be drawn from the registered description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean summarize?

The primary outcome is a continuous measurement, reported in parts per million, and is specified as a mean with standard deviation. In general, a mean is the arithmetic average of the recorded measurements. It gives a compact description of the group's central level, but it does not show whether values cluster closely together or vary widely. The standard deviation describes that spread. Both are useful for describing a continuous outcome, but neither is reported for the week 10 endpoint in the registry record.

A mean can be influenced by unusually high or low observations. For a skewed distribution, the mean may not describe a typical participant especially well. General assessment of the distribution and individual observations can help determine whether a mean and standard deviation are adequate summaries. The registry record does not report the distribution of carbon monoxide measurements or diagnostic checks.

What would a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimated quantity. For a mean, it can show how precisely the population mean is estimated from the observed participants, conditional on the statistical method and assumptions. It is not a range that guarantees where every participant's measurement lies. The registry record does not report a confidence interval or the underlying endpoint summary, so precision cannot be assessed from this record.

A p-value, if reported, would address compatibility between data and a specified null hypothesis under an analysis model. It would not give the size of an effect or its practical importance. No p-value or hypothesis test for the primary endpoint is reported. The record also does not state a statistical analysis plan, so the planned hypothesis, model, covariate adjustments, and handling of repeated measurements are not reported in the registry record.

Why does the single-group design matter?

General: a single-group study can describe outcomes observed among participants receiving an intervention. If measurements are available at more than one time, a paired analysis may describe within-participant change. That change alone does not isolate the intervention's effect, because no concurrent control group shows what might have happened without the intervention. The record specifies one open-label arm and does not report a control comparison.

The word open-label indicates that masking was absent. In general, awareness of treatment can affect participant behavior, reporting, or aspects of assessment. The carbon monoxide outcome is an instrument-based measure, but the registry record does not describe the measurement procedure or whether the assessor was masked. No claim about the presence or absence of bias can be quantified from the information reported.

How should planning illustrations be read?

General: a sample-size calculation uses assumptions about the outcome, target effect, significance level, allocation, and analysis method to illustrate how many participants might be needed under those assumptions. The planning assumptions associated with this record specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The calculations are planning illustrations, not a report of the study's original design.

The enrolled study had one arm, so assumptions about equal allocation between two arms describe a hypothetical planning comparison rather than the trial's actual allocation. The registry record does not report an original sample-size justification or confirm that these assumptions were used when the study was planned. Sample-size illustrations are not observed power, and they do not establish that the study could detect an effect of a particular size. The registry record also does not report the numerical planning outputs in the registry record for this explanation.

Over-dispersion is a general concern for count outcomes when variation exceeds what a simple count model expects. It is not a direct description of the primary continuous carbon monoxide endpoint, and the registry record does not report a count-model analysis. No claim about over-dispersion or a model adjustment is warranted for this study.

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("Enrolled Participants")
n   <- c(12)
m   <- c(9.2)
sp  <- c(6.3)
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  Enrolled Participants  12  9.200  6.300  5.197  13.203

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and identifies carbon monoxide levels as the primary outcome and smoking cessation as a secondary outcome. Considering multiple outcomes can raise a multiplicity question: when several hypotheses are tested, the chance of at least one apparently unusual result can increase. In general, a prespecified outcome hierarchy or an adjustment method can help clarify how multiple tests are interpreted. The registry record does not report a multiplicity strategy, and it does not provide results for the listed outcomes.

The record indicates zero analyses. It does not specify whether this means no analyses were entered into the registry or whether analyses were not conducted. The analysis population, treatment of participants with missing measurements, and methods for handling missing data are not reported in the registry record. The enrollment count alone does not establish how many participants contributed to the week 10 endpoint.

General: missingness can affect interpretation when participants without observed outcomes differ from those with observed outcomes. Analysts may describe missingness, use assumptions about its causes, and conduct sensitivity analyses. None of those details is reported in the registry record. It is therefore not possible to assess whether the posted endpoint summaries, if any, represent all enrolled participants or a subset.

The registry record also does not report a protocol-based analysis population, such as an intention-to-treat or per-protocol population. No such population should be assumed. Without an analysis plan and outcome-level denominators, the completeness and analysis basis of the primary and secondary outcomes remain unclear.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists 23 participants at risk for serious adverse events and zero affected. It lists 23 participants at risk for other adverse events and 17 affected. Deaths are recorded as zero. These are counts of participants in the registry's adverse-event categories; they do not provide detail about event severity beyond the serious-versus-other classification.

No serious adverse-event terms are listed. The record does not give descriptions of the other adverse events, their timing, duration, relationship to treatment, or whether participants experienced more than one event. It also does not report how adverse events were collected or whether follow-up was complete for every participant.

In general, safety counts should be interpreted in light of the number monitored, the observation period, event definitions, and completeness of reporting. The registry's adverse-event figures describe what was entered for this study; they do not establish that no unreported events occurred. They also do not answer the primary carbon monoxide outcome question. The registry record identifies the treatment period as 9 weeks, but does not specify the adverse-event monitoring window.

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

The record establishes that a completed, single-group study enrolled 23 adult smokers willing to quit and used escalating transdermal nicotine patch treatment, with brief counselling for participants who continued to smoke. It identifies week 10 expired carbon monoxide as the primary endpoint and smoking cessation as a secondary outcome. These design details describe what the study set out to assess.

The record does not provide the observed carbon monoxide result or the smoking-cessation result. It therefore does not show whether carbon monoxide levels or cigarette consumption changed, how large any change was, or how uncertain an estimate might be. The expected direction in the brief summary is not a finding. The absence of outcome results is also not evidence that there was no change.

Even with reported pre- and post-treatment outcomes, a single-group study would not establish a treatment effect as directly as a randomized controlled comparison. Without a concurrent control group, other changes over time could contribute to an observed difference. The open-label design is another feature relevant to interpretation, although the record does not provide enough information to quantify its influence.

The adverse-event entries report zero participants with serious adverse events among 23 at risk, 17 participants with other adverse events among 23 at risk, and zero deaths. These figures are limited to the categories and detail entered in the registry. They do not replace the missing efficacy results or provide a complete description of event types.

Overall, the registry record documents the study's design and some safety counts, but it does not provide the primary or secondary outcome findings needed to assess the measured smoking-related outcomes. No conclusion about treatment benefit or lack of benefit follows from the information reported.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a treatment description and a comparative treatment estimate. A single-arm record can describe who was enrolled, what intervention was used, and which measurements were planned. It cannot, by design alone, provide a randomized contrast with a control group. That distinction matters whenever a brief summary presents an expected change that might otherwise be mistaken for a result.

The primary endpoint is an objective continuous measurement, but a defined measurement is not the same as a reported finding. To assess its distribution, central value, variability, and precision, readers need outcome summaries and their analysis basis. The registry record does not report those details. The example illustrates why endpoint definitions and results must be considered separately.

The sample-size illustrations also require context. Their assumptions describe a hypothetical two-arm planning exercise, whereas the actual study had one treatment arm. General statistical planning calculations can inform design under stated assumptions, but they do not retrospectively show that a completed study had adequate power. Nor are they a substitute for observed effect estimates and uncertainty.

Finally, the record's absence of analysis entries, outcome summaries, and missing-data details limits what can be inferred. Statistical transparency includes not only the planned endpoint but also the analysis population, handling of incomplete measurements, and results with uncertainty. Without these elements, readers can describe the design and the recorded safety counts, but cannot evaluate the primary outcome's magnitude or precision.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record supplies limited outcome information. It defines week 10 expired carbon monoxide as the primary endpoint but does not report the observed mean, standard deviation, participant-level denominator, or inferential analysis. It lists smoking cessation as a secondary outcome but does not report a result or its operational definition. The daily cigarette-consumption change mentioned in the brief summary is not accompanied by an outcome estimate.

The study enrolled 23 participants in one open-label arm and had no like-for-like control comparison. This limits causal interpretation and makes it impossible to distinguish an intervention-related change from other changes over time using a between-group contrast. The record does not report masking, outcome assessor procedures, adherence, or details of the dose escalation beyond the general description.

The registry does not report the sample-size justification, statistical analysis plan, analysis population, missing-data approach, or multiplicity plan. It also does not describe the measurement protocol for expired carbon monoxide or give the criteria used to define smoking cessation. These omissions limit assessment of measurement consistency and analysis choices.

Safety reporting is also brief: the record gives participant counts for serious and other adverse events and deaths, but no serious event terms or descriptions of other events. The adverse-event monitoring window and collection procedures are not reported in the registry record. These limitations concern the information available in the registry and do not establish what may have been documented elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Smoking While on Transdermal Nicotine Replacement Therapy: Effects on Craving and Cessation — NCT00289653.
• Registry record last updated 2018-10-05; status last verified 2017-12.
• Results first posted 2018-10-05.
• 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

NCT00289653 is listed as completed, with 23 participants enrolled. It studied adult smokers willing to quit in a single open-label treatment arm using escalating doses of transdermal nicotine patch (Nicoderm) over 9 weeks; brief counselling was given if participants continued smoking. The primary endpoint was expired carbon monoxide at week 10, measured in parts per million. Smoking cessation was listed as a secondary outcome.

The registry reports no analysis entries and does not report the primary or secondary outcome results. Safety counts list zero serious adverse events among 23 at risk, other adverse events in 17 of 23, and zero deaths. The record does not provide event descriptions or further analysis details.