Neural Mechanisms Associated With Risk of Smoking Relapse: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neural Mechanisms Associated With Risk of Smoking Relapse (NCT02837510), a na na study. The primary outcome is Days to Relapse.

2. Clinical Question

In statistical terms, the design can describe outcomes among the participants who entered the quit period and met the specified fMRI completion criteria. Without a randomized comparison group, it cannot isolate the effect of counseling from other influences on relapse timing. Nor does the registry record describe a comparison that would establish whether measured brain changes predict or explain relapse. The endpoint definition and study objective identify what the investigators intended to examine; they do not, by themselves, establish the size or direction of any association.

3. Trial Design

The registry lists this study as completed, with enrollment of 119 and a single-group model. Allocation is recorded as NA and masking as none; the phase is also listed as NA. The sponsor is the University of Pennsylvania. The study start is recorded as 2016-05, and primary completion as 2023-06-01. These registry fields describe administrative and design features, but do not supply a detailed protocol or statistical analysis plan.

Participants received standard smoking cessation counseling. The study included a pre-treatment fMRI session during abstinence and another during smoking, with a washout period identified as two weeks between sessions. Participants then entered a quit attempt followed for six months. The registry description says the study examines how abstinence-induced brain changes contribute to cessation outcomes. Brain activation measured as BOLD percent signal change is listed as a secondary outcome. The record identifies two outcome measures but reports no analyses.

The primary outcome population was restricted to participants who completed both fMRI sessions and started the quit period. The number meeting those criteria is not reported in the registry record. The study’s single-group structure means that its outcomes are not a randomized contrast between counseling and an untreated or alternative-treatment group. The registry record also does not report a protocol-level explanation for the absence of a comparator, details of counseling delivery, or a sample-size justification.

Planning illustrations based on an observed effect are not the study’s actual design. Their stated assumptions include a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. Those assumptions do not turn this single-group study into a two-arm comparison, and the illustrations are not observed power. The outcome estimate on which such illustrations depend is not reported in the registry record.

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: After study intake participants were randomized to one of two scan order: Abstinent then Smoking, Smoking then Abstinent.

1st Pretreatment fMRI Session

Reasons for not completing this period:

Washout (2 Weeks)

Reasons for not completing this period:

2nd Pretreatment fMRI Session

Reasons for not completing this period:

Quit Attempt (6 Months)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants completing both fMRI sessions (smoking, abstinent) and starting the quit period were included in the analysis.

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 Days to Relapse, measured over 6 months after target quit date.

The primary endpoint is the number of days from the target quit date to the first day of a relapse period, with the outcome assessed over the six months after the target quit date. Relapse was defined using either biochemical verification of smoking or seven consecutive days of smoking based on self-report. Daily smoking reports were collected using a validated timeline follow-back method. The registry description also states that abstinence was checked weekly using urine cotinine and a carbon monoxide reading.

The endpoint is expressed as a mean with a standard deviation. In general, days to relapse represents the timing of an event, while a mean and standard deviation describe the average observed timing and the spread of values around that average. This can provide an interpretable summary of when relapse occurred in the analyzed group, but it does not by itself describe the full pattern of event timing or account for differences between groups.

The registry’s endpoint rule treats drop-outs as relapsers following the last date for which abstinence data were provided. This rule makes follow-up loss part of how the endpoint is defined, rather than simply removing those participants from the outcome description. The record does not report the resulting mean, standard deviation, number of relapses, or analysis population count. Accordingly, the endpoint definition is available, but its observed value and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. The listed outcome is days to relapse, with the interval beginning at the target quit date. The endpoint description supplies a relapse rule and a follow-up window, but the record does not report the statistical procedure used to estimate the mean or standard deviation. It also does not report any model used to account for participant characteristics, repeated observations, or incomplete follow-up.

What do the mean and standard deviation describe?

General explanation: a mean is an average of measured values. A standard deviation describes how dispersed those values are around the mean. For days to relapse, the mean would describe average time to the defined relapse event among the analyzed participants, while the standard deviation would describe variation in those times. These summaries do not show the shape of the data distribution or whether some participants had substantially different follow-up experiences. The registry record does not give either summary statistic.

The endpoint concerns time until an event, but the registry lists its parameter as a mean and dispersion as a standard deviation. Some time-to-event methods can incorporate participants whose event time is not observed during follow-up, rather than treating every such observation as a fully observed event time. Whether such methods were used is not reported in the registry record. The specified drop-out rule instead states that participants are considered relapsers following the last date of abstinence data provided. The record does not describe a sensitivity analysis to assess alternative assumptions for missing outcome information.

How is relapse defined?

The registry description defines relapse as either a positive biochemical verification of smoking or seven consecutive days of smoking based on self-report. Time to relapse is measured from the target quit date to the first day of the relapse period. Daily self-reported smoking data were collected using a validated timeline follow-back method, and abstinence was to be verified weekly using urine cotinine and a carbon monoxide reading. These details specify how the endpoint was intended to be determined. They do not report how many participants relapsed, when events occurred, or whether verification data were complete.

What do the planning assumptions mean?

General explanation: a sample-size calculation estimates how many observations might be needed to detect a chosen effect under stated assumptions. The registry’s planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also describes detecting a stated fraction of an observed effect. These are assumptions for a planning illustration, not a report of the study’s actual allocation or an observed power calculation. The actual trial is listed as single-group with allocation NA. The registry record does not report the observed effect value or the numerical planning results.

For a two-arm comparison, a planning result may be expressed as participants per arm for 80% power, or participants per arm for 90% power. Such figures depend on the effect size and other assumptions; they do not indicate how much power the completed study actually had. In this study, a hypothetical two-arm calculation cannot establish the precision of a single-group outcome or supply a missing randomized comparator. The registry record does not report the primary outcome estimate needed to interpret an effect-based planning illustration.

Why does over-dispersion matter in general?

General explanation: over-dispersion occurs when data vary more than a statistical model expects. If a model assumes less variability than is present, uncertainty may be understated and inferential results may appear more precise than warranted. Conversely, a model that accommodates variability appropriately can better reflect uncertainty. This is a general statistical consideration, not a feature established for this study: the registry record does not report a model for count data or an assessment of over-dispersion. Because the primary outcome is described as continuous, the record does not provide grounds to say that over-dispersion was assessed or relevant to the reported analysis.

The registry record lists two outcome measures and zero analyses. It does not report methods for confidence intervals, hypothesis testing, covariate adjustment, handling of multiple outcomes, interim monitoring, or the choice of a primary analysis model. These elements are necessary to understand how an estimate would be derived and how uncertainty would be quantified, so their absence limits independent statistical interpretation.

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("Abstinent Then Smoking", "Smoking Then Abstinent")
n   <- c(58, 55)
m   <- c(3.95, 3.78)
sp  <- c(2.67, 2.69)
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  Abstinent Then Smoking  58  3.950  2.670  3.248  4.652
CARM  Smoking Then Abstinent  55  3.780  2.690  3.053  4.507

11. Multiplicity, Missing Data and Analysis Populations

The record lists two outcome measures: days to relapse as the primary outcome and brain activation measured as BOLD percent signal change as a secondary outcome. It does not report the number of statistical tests performed for these measures, any testing hierarchy, or a procedure for controlling multiplicity. Although zero analyses are listed, the registry record does not describe whether analyses were conducted outside the posted registry results.

General explanation: when several outcomes or comparisons are tested, the chance of at least one apparently notable result can increase if each test is interpreted without regard to the others. A prespecified hierarchy or adjustment can address that issue, but neither is reported in the registry record. The record also does not report interim analyses or stopping rules; their use should not be inferred from their absence.

The primary analysis population was defined as people completing both fMRI sessions and starting the quit period. Its size is not reported. Enrollment is listed as 119, but this total does not establish how many participants were included in the primary analysis. The registry describes drop-outs as relapsers after their last date of abstinence data, but does not report the number of participants with missing data, the amount of follow-up available, or sensitivity analyses using other missing-data assumptions.

The registry record does not report a statistical analysis plan, details of exclusions, the handling of other incomplete measurements, or whether all enrolled participants were analyzed as intended. Those omissions prevent assessment of how missingness and multiplicity may have affected the reported evidence.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hospitalization (0.9%), hypoglycemic event (0.9%), hospitalization (0.9%).

The registry lists serious adverse event information by study stage. The pre-treatment fMRI abstinent session records 117 at risk, zero serious events, zero other events, and zero deaths. The two-week washout records 117 at risk, zero serious events, one other event, and zero deaths. The pre-treatment fMRI smoking session records 115 at risk, zero serious events, one other event, and zero deaths. The six-month quit attempt records 113 at risk, four serious events, zero other events, and zero deaths.

The listed top serious-event terms are Hospitalization at 0.9%, Hypoglycemic event at 0.9%, and hospitalization at 0.9%. The capitalization of the hospitalization terms differs in the registry listing; the record does not explain whether they represent distinct categories or duplicate descriptions. These terms should therefore be read as recorded, without combining or reclassifying them.

General explanation: counts at risk identify the group denominator for a stage, while event counts describe recorded events within that stage. The registry record does not provide further detail about event timing, duration, relationship to study procedures, or participant-level overlap. These safety figures describe reported events and are not, on their own, a comparative assessment, especially given the single-group design.

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

The registry record supports a description of the study’s aims, design, endpoint definition, and recorded safety counts. It does not report the primary outcome estimate or any analysis results. Thus, it cannot establish the average number of days to relapse in the analyzed population, the spread of relapse times, or the precision of an estimate. It also does not report numerical results for the secondary brain-activation outcome.

The study’s objective is to examine how abstinence-induced brain changes relate to smoking-cessation outcomes. An objective is not a result. Without reported brain-activation estimates and an analysis of their relationship to relapse, the registry does not show whether such a relationship was observed, its direction, or its size. Nor does it establish that brain changes caused any difference in relapse timing.

The single-group design permits description of participants who received counseling, but it does not provide a randomized comparison with another treatment or control group. The posted record therefore cannot estimate a causal treatment contrast from random allocation. This does not show that counseling had no effect; it means the registry’s design and reported results do not provide that kind of comparative evidence.

General explanation: statistical uncertainty is usually conveyed through an interval or another measure of precision, interpreted alongside the estimate and assumptions of the analysis. Those outcome summaries are not reported in the registry record. Planning illustrations are distinct from results: they use assumptions to explore hypothetical sample-size needs and are not observed power or evidence of an effect. A reader should not treat such calculations as a substitute for outcome estimates, uncertainty intervals, or a control comparison.

The safety entries document serious events during the listed stages, including four serious events in the six-month quit attempt stage and no deaths in the listed groups. These counts do not, by themselves, establish whether events were caused by study participation or how rates would compare with another group. Overall, the record describes what investigators planned to measure and some safety reporting, but does not provide the results needed to judge the primary scientific question.

14. Why This Trial Matters Statistically

This study raises a statistical question at the intersection of repeated measurement and clinical follow-up: whether brain activity measured during smoking and abstinence is associated with a later cessation outcome. The registry identifies both the fMRI sessions and days to relapse, making the intended connection between a biological measure and a clinical event clear. The statistical challenge is not simply to report measurements separately, but to specify how their relationship is estimated and how uncertainty is handled.

The study also illustrates why an endpoint’s operational definition matters. Relapse can be identified through biochemical verification or a sustained period of self-reported smoking, and the event date is defined as the first day of the relapse period. Drop-outs are assigned a relapse time after the last date of abstinence data. Such rules shape the outcome being summarized and affect how incomplete follow-up is represented.

At the same time, the single-group structure places an important boundary on interpretation. Outcomes within a counseling group can be described, but a randomized treatment contrast is not available from this design. For clinical researchers, distinguishing a group’s observed outcome from a comparative treatment effect is essential. Neither the study objective nor an effect-based planning illustration changes that distinction.

Finally, a registry record that states an endpoint but does not report its estimate illustrates the difference between design information and evidence about outcomes. Without the outcome summary, analysis population count, and uncertainty measures, the central statistical result cannot be evaluated. The value of the registry entry is therefore in documenting the question and methods that were intended, while its missing analysis results limit conclusions about what the study found.

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 most consequential limitation for interpreting this record is that it reports no analyses and no primary outcome estimate. The record identifies days to relapse as the primary endpoint but provides no mean, standard deviation, confidence interval, or test result. It also does not report the numerical results for the secondary brain-activation outcome or any analysis connecting that measure with relapse.

The study is listed as single-group, with allocation NA and masking none. There is no randomized comparison group in the registry record, so the listed design cannot furnish a randomized contrast between counseling and another condition. This limits causal interpretation of outcomes observed among participants receiving counseling.

The analyzed population is defined by completion of both fMRI sessions and initiation of the quit period, but its size is not reported. Although enrollment is listed as 119, the number included in the primary analysis cannot be determined from that total. The registry describes a rule for drop-outs but does not give the number of drop-outs or show how alternative missing-data assumptions might change the outcome summary.

The record does not report a statistical analysis plan, sample-size justification, analysis model, interim analysis procedures, multiplicity approach, or confidence-interval method. It also does not report detailed counseling delivery or further context for the serious adverse events. These absences limit assessment of analysis choices and generalizability; they should not be replaced by assumptions about what the protocol may have specified.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Neural Mechanisms Associated With Risk of Smoking Relapse — NCT02837510.
• Registry record last updated 2025-03-05; status last verified 2025-02.
• Results first posted 2025-03-05.
• 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

The completed study enrolled 119 participants and is listed as a single-group study of standard smoking cessation counseling, with masking none and allocation NA. The primary endpoint was days from the target quit date to relapse, assessed over six months. The primary analysis population was defined as participants completing both smoking and abstinent fMRI sessions and starting the quit period.

Brain activation measured as BOLD percent signal change was listed as a secondary outcome. The registry reports stage-specific safety counts, including four serious events during the six-month quit attempt and zero deaths in the listed groups. It lists zero analyses and does not report a primary outcome estimate, a numerical brain-activation result, or the size of the primary analysis population. The record therefore documents the study question and endpoint definitions, but not the results needed to quantify the primary outcome or its precision.