Maintaining Nonsmoking: Older Smokers - 1: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Maintaining Nonsmoking: Older Smokers - 1 (NCT00086385), a randomized phase 3 study. The primary outcome is Participants Abstinent From Cigarettes.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, parallel-group trial with no masking. The registry lists enrollment of 403 participants and the status as completed. It gives the study start as 2001-09 and primary completion as 2009-03. The brief study summary says the purpose was to examine pharmacological and psychological interventions for smokers over 50.

Four treatment arms are represented in the outcome results: Brief Treatment, Extended NRT, Extended Tailored Counseling + NRT, and Tailored/No Extended NRT. The reported arm sizes for the primary outcome are 100, 99, 104, and 99 participants, respectively. The treatment descriptions indicate that Brief Treatment combined medication, NRT, and group counseling. Extended NRT involved continuing NRT following the brief treatment period; the registry description says participants would be encouraged to continue through Week 24. Tailored/No Extended NRT is described as identical to the tailored NRT condition except that NRT was unavailable after Brief Treatment. The full description of Extended Tailored Counseling + NRT is truncated in the registry record, so its complete schedule and content are not reported there.

Random allocation supports comparisons among assigned groups, but the record does not provide details of the allocation sequence, concealment, or implementation. It also does not report the trial's original sample-size justification or complete statistical analysis plan. The posted outcome material gives arm counts and pairwise comparisons with Brief Treatment, rather than a full account of every planned analysis. The outcome timeframe is described as two years, and the primary endpoint is specifically assessed at week 104.

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: One participant died at week 5 before randomization.

Overall Study

Reasons for not completing this period:

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 Participants Abstinent From Cigarettes, measured over Two years.

The primary endpoint is the number of participants abstinent from cigarettes, defined in the registry as 7-day point prevalence cigarette abstinence verified biochemically at week 104. Point prevalence describes abstinence during a specified recent period rather than continuous abstinence throughout the entire follow-up. Biochemical verification is used to corroborate reported abstinence, although the registry record does not specify the verification method or threshold.

This endpoint is useful for comparing treatment groups at a common follow-up point. It expresses the outcome as a binary status for each participant: meeting or not meeting the stated abstinence definition at the assessment. The posted results therefore report counts by arm and comparisons of the proportions represented by those counts. They do not indicate how long participants had remained abstinent before the assessment, whether abstinence was uninterrupted, or what happened after week 104.

The endpoint provides a focused measure of smoking status at the two-year assessment, but it captures only one aspect of treatment experience. The registry record lists one outcome measure and does not post secondary outcomes. Details about missing endpoint assessments, the handling of participants whose status could not be verified, or any other endpoint rules are not reported in the registry record.

7. Results Posted in the Registry

• Extended NRT: 35.4% (35/99) versus 31.0% (31/100) on control; risk difference 4.4 percentage points (95% CI -8.7 to 17.4), risk ratio 1.14 (0.77–1.69); unadjusted two-proportion z-test p = 0.514.
• Extended Tailored Counseling + NRT: 37.5% (39/104) versus 31.0% (31/100) on control; risk difference 6.5 percentage points (95% CI -6.5 to 19.5), risk ratio 1.21 (0.82–1.78); unadjusted two-proportion z-test p = 0.328.
• Tailored/No Extended NRT: 45.5% (45/99) versus 31.0% (31/100) on control; risk difference 14.5 percentage points (95% CI 1.1 to 27.8), risk ratio 1.47 (1.02–2.11); unadjusted two-proportion z-test p = 0.036.

8. Statistical Interpretation

9. Statistical Methods Explained

Binary outcomes and arm-level counts

The primary outcome is binary: participants either met the registry's definition of abstinence at week 104 or did not. For each arm, the posted results give the number of participants and the number recorded as abstinent. This makes the outcome interpretable as a count and as a proportion of the arm. The comparisons then express differences between each treatment arm and Brief Treatment.

Risk difference

A risk difference subtracts the outcome proportion in the reference group from the outcome proportion in the comparison group. It is expressed on the probability scale, so a value of 0 represents no difference. A positive estimate means the observed outcome proportion was higher in the comparison group; a negative estimate means it was lower. The risk difference is often useful because it describes an absolute contrast, rather than a relative one. The posted estimates are 0.043 for Extended NRT, 0.065 for Extended Tailored Counseling + NRT, and 0.144 for Tailored/No Extended NRT, each compared with Brief Treatment.

Risk ratio and odds ratio

A risk ratio compares the outcome proportions by division. A value of 1 represents equal proportions; values greater than 1 indicate a higher proportion in the comparison group, and values below 1 indicate a lower proportion. An odds ratio compares odds rather than proportions. Odds and probabilities are related but are not the same quantity, so these measures have different interpretations. The record includes risk-ratio and odds-ratio estimates and intervals for each comparison. The risk difference is the main contrast used in the posted comparison results.

Confidence intervals

A confidence interval describes statistical uncertainty around an estimate under the assumptions of the method used. It gives a range of values compatible with the observed data and that method. A narrower interval indicates greater precision; a wider interval indicates less precision. For a risk difference, an interval containing zero is compatible with no difference as well as with differences in either direction. An interval entirely above or below zero excludes no difference at the interval's stated confidence level, subject to the analysis assumptions. Confidence intervals do not show the probability that a particular effect is true, and they do not address every source of uncertainty, such as bias or missing outcomes.

Unadjusted p values

The posted p values are labeled unadjusted. In general, a p value measures how unusual results at least as incompatible with a no-difference model would be under that model and the test assumptions. It is not the probability that the no-difference model is true, nor a measure of the size or practical importance of an effect. An unadjusted p value does not account for examining multiple comparisons. The registry record does not report a multiplicity adjustment or the specific testing procedure used for the posted p values.

Counts and dispersion

The outcome is a participant count arising from a binary status, rather than a continuous measurement. The posted arm-level results include a spread value, but the registry record does not explain its definition. It should not be interpreted as a confidence interval unless the record states that it is one. In general, over-dispersion is relevant when observed variability in count data exceeds what a chosen count model expects. It is not a separate feature to assume for these binary participant outcomes, and the record does not report a model addressing over-dispersion.

Analysis and design details

The registry identifies randomization, a parallel model, and no masking. These design labels do not by themselves specify how the outcome comparisons were calculated. The detailed analysis methods, analysis populations, covariate adjustments, handling of missing outcomes, and original sample-size justification are not reported in the registry record. The posted results are therefore best read as the listed arm counts and unadjusted pairwise estimates, with uncertainty described by their confidence intervals.

10. Confidence Intervals and Precision

Precision is reflected in the width of the confidence intervals around the risk differences. For Extended NRT versus Brief Treatment, the estimate is 0.043 and the interval is -0.087 to 0.174. For Extended Tailored Counseling + NRT versus Brief Treatment, the estimate is 0.065 and the interval is -0.065 to 0.195. Each interval includes zero and spans effects on both sides of no difference. The data therefore do not pin down the direction or size of these contrasts precisely.

For Tailored/No Extended NRT versus Brief Treatment, the estimate is 0.144, with an interval from 0.011 to 0.278. The interval lies above zero, but it still covers a range of possible effect sizes. The point estimate should not be treated as the exact underlying difference; the interval is an important part of interpreting it.

Confidence intervals quantify sampling uncertainty under the statistical method's assumptions. They do not account for every possible source of uncertainty, including incomplete outcome data, measurement limitations, or unreported analysis choices. The registry record does not report the detailed methods used to calculate these intervals, or how missing observations were handled. As a result, their interpretation should remain tied to the posted comparisons and the stated endpoint.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on each comparison's observed effect, not the trial's original design assumptions. They give participants per arm for the listed binary-outcome comparisons; they are not totals across arms and do not represent total event counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The registry record does not report the trial's own original sample-size assumptions.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under the planning assumptions, if that effect is present and the assumptions hold. The 90% power column gives the corresponding number for a higher chance of detection under those assumptions. These are design calculations, not guarantees about any future trial. They do not describe the probability that the observed result is true.

Rows for planning for 75% or 50% of the observed effect use smaller target effects than the full observed estimate. Smaller effects require more participants to detect at the same power and significance level, which is why the planning figures increase as the target effect is reduced. The illustrations use effects observed in this trial, which may not be stable estimates of an underlying treatment effect. This is not observed power; observed results are described by their estimates, confidence intervals, and p values.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.310; treatment proportion p₁ = 0.354; average p̄ = 0.332.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6659 = 1.3051.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6652 = 0.5598.
4. n = (1.3051 + 0.5598)² / (0.0435)² = 1,835.0, rounded up to 1,835 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.31                          # control proportion
p1 <- 0.353535353535354                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(86385)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 1,835 (80% power), 2,457 (90% power)
 75% of observed effect: n per arm = 3,236 (80% power), 4,332 (90% power)
 50% of observed effect: n per arm = 7,219 (80% power), 9,663 (90% power)
power.prop.test: 1835 
Simulated power at n = 1,835 per arm: 0.797 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The posted results include three comparisons with Brief Treatment. The registry record does not report whether these were the only planned comparisons, whether an overall test was conducted, or whether any multiplicity procedure was used. The listed p values are unadjusted. When several hypotheses are tested, the chance of at least one apparently unusual result can increase; adjustment methods can address that issue, but no such method is reported. The p value of 0.036 for Tailored/No Extended NRT is therefore an unadjusted result and should be interpreted in that context.

The record does not report a detailed missing-data plan, the number of participants with unavailable week 104 assessments, or how such outcomes were treated in the posted analysis. The arm sizes and abstinent counts are given, but they do not establish whether every randomized participant had an observed outcome or whether the analysis included all randomized participants. The handling of participants who withdrew, could not be contacted, or lacked biochemical verification is not reported in the registry record.

Analysis-population definitions are also not reported. The record does not state whether results are based on intention-to-treat, per-protocol, or another population, nor does it describe exclusions after randomization. The posted comparisons should not be assigned one of these labels without that information.

These omissions limit assessment of the analysis beyond the posted counts and estimates. They do not establish that missingness or multiplicity procedures were absent from the trial's original analysis; they mean that the relevant details are not reported in the registry record. The available results can be interpreted as posted, while the effects of unreported analysis choices remain uncertain.

14. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death (not related to study) (2.0%), angina (1.0%), heart procedure (1.0%), implantation of an automatic implantable cardioverter defibrillator (1.0%), fatigue, weakness, and unsteady walking (1.0%).

The serious adverse event figures give the number affected and the number at risk in each arm. Brief Treatment had 2 affected participants among 100 at risk; Extended NRT had 5 among 99; Extended Tailored Counseling + NRT had 4 among 104; and Tailored/No Extended NRT had 2 among 99. These are descriptive arm-level counts. The record does not provide comparative confidence intervals or tests for these safety counts.

The registry also lists serious event terms, including Death (not related to study) at 2.0%, and Angina, Heart Procedure, Implantation of an Automatic Implantable Cardioverter Defibrillator, Fatigue, Weakness, and Unsteady Walking, and Asthma Attack, each at 1.0%. These terms should be read as the listed serious-event terms, not as a complete description of every event or as a comparison among treatments. Death counts by treatment group are not reported in the registry record.

Differences in observed counts alone do not show that an intervention caused an event or changed risk. Interpretation also depends on event definitions, follow-up, attribution, and completeness of reporting; those details are not reported in the registry record.

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

The results describe the number of participants meeting a specific abstinence definition at week 104 in each randomized treatment arm. The observed counts were 31 of 100 for Brief Treatment, 35 of 99 for Extended NRT, 39 of 104 for Extended Tailored Counseling + NRT, and 45 of 99 for Tailored/No Extended NRT. The pairwise risk differences and confidence intervals quantify the observed contrasts with Brief Treatment and the uncertainty around them.

Two comparisons have intervals that include no difference: Extended NRT and Extended Tailored Counseling + NRT. The Tailored/No Extended NRT comparison has a positive posted risk difference and a confidence interval from 0.011 to 0.278, with an unadjusted p value of 0.036. This describes the posted comparison; the record does not report adjustment for multiple comparisons. The results do not establish which treatment component, if any, explains the observed pattern.

The endpoint is 7-day point prevalence abstinence at one assessment, verified biochemically. It does not measure continuous abstinence through the full follow-up, duration of abstinence, or later smoking status. The results also do not by themselves establish how treatment effects might differ across participant subgroups, because subgroup results are not posted.

These findings should not be generalized beyond the study population and outcome without additional evidence. Details about participant eligibility, missing outcomes, analysis populations, and full treatment schedules are incomplete or not reported in the registry record. The arm counts and comparisons are informative as posted, but they do not answer every question about treatment effects, safety, or the reasons participants did or did not meet the endpoint.

16. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison should be read through both its point estimate and its uncertainty. A positive risk difference is an estimate of the contrast in observed outcome proportions, while the confidence interval indicates how much uncertainty remains. In this study, the two comparisons involving extended NRT have intervals that include no difference and allow effects in either direction. The Tailored/No Extended NRT comparison has an interval above zero, but its estimate still has meaningful uncertainty.

The results also demonstrate the importance of distinguishing absolute and relative measures. A risk difference describes an absolute contrast, whereas a risk ratio and odds ratio describe relative contrasts on different scales. These measures can offer complementary perspectives, but they are not interchangeable. The posted binary counts make the outcome easy to identify, while the confidence intervals and unadjusted p values add information about uncertainty and statistical compatibility.

Multiplicity and missing-data reporting matter to interpretation. The registry record lists several arm comparisons but does not report a multiplicity approach, detailed missing-outcome handling, or analysis-population definitions. Those gaps do not invalidate the posted figures, but they limit how fully their statistical context can be assessed. The sample-size illustrations also show how planning depends on the effect targeted: a smaller target effect requires more participants under the stated assumptions. Together, these features make the trial useful for understanding the distinction between observed results, inferential uncertainty, and design planning.

17. 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 gives only a partial account of the intervention schedules. In particular, the description of Extended Tailored Counseling + NRT is truncated, and the Extended NRT description ends before all conditions are clear. The complete content, timing, and adherence expectations for those regimens are therefore not reported in the registry record. This limits detailed interpretation of which treatment components distinguish the arms.

The primary outcome is a single assessment of 7-day point prevalence abstinence at week 104. The record does not report continuous abstinence, repeated assessments over follow-up, or outcomes beyond that assessment. It also does not identify the biochemical verification method or explain the posted spread values for the arms.

Analysis details are limited. The registry record does not report the original sample-size justification, a complete statistical plan, analysis-population definitions, missing-data handling, or a multiplicity procedure. It does not report detailed information about allocation concealment or how randomization was implemented. These limitations make it difficult to assess the effect of analysis choices or the sensitivity of the comparisons to unobserved outcomes.

The reported results are limited to the primary outcome and the posted safety summaries. The registry indicates no secondary outcomes posted. As a result, the record does not support broader conclusions about other outcomes, subgroup differences, or the full balance of benefits and harms.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Maintaining Nonsmoking: Older Smokers - 1 — NCT00086385.
• Registry record last updated 2015-03-23; status last verified 2015-03.
• Results first posted 2013-10-10.
• 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.

21. Record Summary

NCT00086385 is a completed, randomized, parallel-group Phase 3 trial with no masking. It enrolled 403 participants and examined pharmacological and psychological approaches for smokers over 50. The four reported arms were Brief Treatment, Extended NRT, Extended Tailored Counseling + NRT, and Tailored/No Extended NRT.

The primary outcome was the number of participants abstinent from cigarettes, defined as biochemically verified 7-day point prevalence abstinence at week 104. The posted comparisons use Brief Treatment as the reference. The risk-difference estimates are 0.043 for Extended NRT, 0.065 for Extended Tailored Counseling + NRT, and 0.144 for Tailored/No Extended NRT. The first two confidence intervals include no difference; the third interval is 0.011 to 0.278, with an unadjusted p value of 0.036.

The record also reports serious adverse event counts by arm and planning illustrations based on observed effects. Several details about analysis methods, missing outcomes, and full intervention descriptions are not reported in the registry record.