Cognitive Remediation With D-Cycloserine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cognitive Remediation With D-Cycloserine (NCT01399866), a randomized phase 3 study. The primary outcome is Effect of D-cycloserine + Cue-exposure Treatment on Continuous Abstinence From Tobacco Smoking..

2. Clinical Question

3. Trial Design

The registry identifies this as a completed phase 3 randomized trial with a parallel-group design and triple masking. The two study arms were placebo and D-cycloserine; both were paired with cue-exposure treatment. The medication descriptions specify the same dose and schedule in both arms: a 50 mg oral capsule, given as a single dose twice, one week apart. The registry record does not report the identities of the masked parties or the procedures used to maintain masking.

Participants were first to prepare for a quit attempt using nicotine replacement therapy or varenicline. The summary says the choice depended on participant preference and medical contraindications. Recently abstinent participants referred by a smoking cessation clinic, a primary care provider, or themselves were to have abstinence confirmed by expired-air carbon monoxide. Participants also needed to demonstrate 18-24 hours of abstinence before the first cue-exposure treatment visit to be eligible for randomization.

The planned schedule included two cue-exposure treatment visits, five to nine days apart, followed by two follow-up visits. The registry describes follow-up at 2-4 days and four weeks after the last treatment visit, and says the full study was expected to last approximately ten weeks. The registry’s primary outcome timeframe is listed as up to 6 weeks. These descriptions do not explain how the visit schedule maps to the primary assessment time point.

The registry lists enrollment as 150, while its study summary describes a plan to enroll 175 eligible participants with an aim of randomizing 60. The posted primary outcome groups contain 32 placebo participants and 30 D-cycloserine participants. The relationship between the enrollment entry, the summary’s planned numbers, and the numbers in the posted outcome groups is not explained in the registry record. The study start is listed as 2011-05 and primary completion as 2013-10.

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: Participants received their choice of nicotine patch or varenicline (0.5 mg per day for 3 days, 0.5 mg bid for 4 days, 1 mg bid for 4 wks) and weekly cognitive behavioral therapy for smoking cessation.

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.

Population: After 4 wks of smoking cessation treatment and CBT, participants who had 18 hrs of abstinence, smoking no cigarettes for at least 18 hrs and CO\<10ppm were randomized

6. Primary Endpoint

The registry lists the primary outcome as Effect of D-cycloserine + Cue-exposure Treatment on Continuous Abstinence From Tobacco Smoking., measured over Up to 6 weeks.

The primary endpoint is continuous abstinence from tobacco smoking, expressed as the percentage of participants meeting the abstinence outcome. The registry says abstinence was assessed using self-report and saliva cotinine measurements. It frames the question as whether the D-cycloserine plus cue-exposure group maintained abstinence better than the placebo plus cue-exposure group at week 6 follow-up, while listing the endpoint timeframe as up to 6 weeks.

Continuous abstinence differs from a measure that captures smoking at only one instant: it is intended to represent ongoing abstinence across the specified assessment period. That makes it relevant to a study focused on preventing return to smoking after a quit attempt. Self-report and a biological measurement are both named in the registry description, but the exact rules for combining them, defining an abstinent participant, and handling conflicting assessments are not reported in the registry record.

The posted arm summaries give 9.0 for placebo and 30.0 for D-cycloserine, with 32 and 30 participants, respectively. The registry identifies the unit as percentage of participants. The accompanying risk-difference estimate is 0.206, with a confidence interval from 0.014 to 0.399. Those figures describe the observed group contrast and its statistical uncertainty; they do not by themselves establish how the outcome was adjudicated or whether all randomized participants were included.

The endpoint is clinically interpretable as an abstinence outcome, but its meaning depends on the assessment period and operational definition. The registry provides the broad measurement sources and follow-up timeframe, while detailed endpoint rules are not reported in the registry record.

7. Results Posted in the Registry

• D-cycloserine: 30.0% (9/30) versus 9.4% (3/32) on control; risk difference 20.6 percentage points (95% CI 1.4 to 39.9), risk ratio 3.20 (0.96–10.71); unadjusted two-proportion z-test p = 0.040.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Effect of D-cycloserine + Cue-exposure Treatment on Skin Conductance

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • D-cycloserine: mean 0.18 versus 0.14 on control; difference 0.04 (95% CI -0.15 to 0.23), standardized effect d = 0.10; z-test p = 0.686.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between D-cycloserine and the control. The interval gives the range of effects that remain compatible with the data.

Effect of D-cycloserine + Cue-exposure Treatment on Heart Rate

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • D-cycloserine: mean 0.98 versus -0.13 on control; difference 1.11 (95% CI -0.13 to 2.35), standardized effect d = 0.44; z-test p = 0.079.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between D-cycloserine and the control. The interval gives the range of effects that remain compatible with the data.

Effect of D-cycloserine + Cue-exposure Treatment on Electromyogram

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • D-cycloserine: mean 0.46 versus 0.25 on control; difference 0.21 (95% CI -0.44 to 0.86), standardized effect d = 0.16; z-test p = 0.526.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between D-cycloserine and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists five secondary outcomes, covering physiological responses, craving, and attentional bias. Numerical results are posted for three of those outcomes: skin conductance, heart rate, and electromyogram. Numerical results for craving and attentional bias are not reported in the registry record. The registry also lists two ANOVA p-values for skin conductance without enough model detail to establish how the analyses differ.

Across the three outcomes with posted arm summaries, the mean-difference intervals include 0. The accompanying unadjusted p-values do not provide a consistent pattern of strong separation between groups. The posted estimates and intervals therefore offer limited precision about whether D-cycloserine changed these secondary measures relative to placebo. They address physiological and related responses, rather than directly duplicating the primary abstinence endpoint.

These secondary findings do not replace the primary result. A physiological response or craving measure may be relevant to a proposed treatment process, but the registry does not report a formal mediation analysis or an analysis linking changes in these measures to abstinence. The secondary results cannot establish that any such measure explains the primary group contrast.

Unadjusted secondary results carry less weight when several outcomes or analyses are considered, because repeated testing increases the chance of at least one nominally unusual result even when no real group differences exist. General statistical explanation: multiplicity procedures can control that chance, but they need to be chosen and reported in relation to the planned family of tests. The registry record does not report a multiplicity adjustment or identify which secondary outcomes were confirmatory. The secondary results are best read as exploratory evidence whose interpretation depends on the missing analysis-plan details.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Effect of D-cycloserine + Cue-exposure Treatment on Skin Conductance
• Effect of D-cycloserine + Cue-exposure Treatment on Heart Rate
• Effect of D-cycloserine + Cue-exposure Treatment on Electromyogram
• Effect of D-cycloserine + Cue-exposure Treatment on Craving
• Effect of D-cycloserine + Cue-exposure Treatment on Attentional Bias Toward Smoking Cuesmeasured With the Emotional Stroop Task

9. Statistical Interpretation

10. Statistical Methods Explained

The outcome is binary at the participant level: each participant either meets the registry’s continuous-abstinence definition or does not. General statistical explanation: binary outcomes can be summarized as the proportion meeting the outcome in each group, then compared using absolute or relative measures. The registry describes the primary result as percentage of participants and posts a risk difference, a risk ratio, and an odds ratio. The detailed primary analysis method is not reported in the registry record.

What does the risk difference express?

The risk difference compares the outcome proportions by subtracting one group’s proportion from the other in a defined direction. It is an absolute contrast, so its scale is tied to the outcome proportion rather than a multiplicative comparison. The posted estimate is 0.206, with a confidence interval from 0.014 to 0.399. Interpreting the sign requires knowing the stated arm order; the registry comparison identifies D-cycloserine as the arm contrasted with placebo, and the posted arm values are higher for D-cycloserine.

The risk ratio expresses the outcome proportion in one group relative to the other. The posted value is 3.2, with a confidence interval from 0.956 to 10.71. The odds ratio compares odds rather than probabilities; its posted value is 4.143, with a confidence interval from 0.999 to 17.18. Odds and probabilities are related but are not the same quantity. Relative measures can appear large even when an absolute contrast is more moderate, so the scale and interval should be considered together. General statistical explanation: a ratio of 1 represents equal values between groups, whereas a difference of 0 represents no absolute difference.

What does the p-value tell the reader?

The unadjusted p-value posted for the primary comparison is 0.04. General statistical explanation: a p-value describes how unusual data at least as discrepant as the observed data would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, and it does not describe the size or importance of an effect. The registry record does not report the complete primary test specification, the significance threshold selected for the trial, or whether the posted p-value comes from the trial’s prespecified analysis.

The registry also gives reported ANOVA analyses for some secondary outcomes. ANOVA is a method for comparing means across groups under its model assumptions. The record does not report the full model specifications, including whether repeated measurements or other covariates were included. For those outcomes, posted arm means and standard deviations provide descriptive information, while the reported ANOVA p-values provide tests whose full interpretation depends on details not reported in the registry record.

Why do confidence intervals matter?

A confidence interval gives a range of estimates compatible with the observed data under the method used to calculate it. General statistical explanation: intervals express uncertainty in the estimated effect, and their width reflects both the data and the estimation procedure. The primary risk-difference interval is entirely above 0, while its relative-measure intervals are broad and extend to values near the no-difference point for ratios. The registry record does not state the confidence level or the exact calculation method for the primary comparison. The interval should therefore be interpreted as posted, without assuming additional details about its construction.

For the continuous secondary outcomes, the posted comparisons are mean differences, accompanied by confidence intervals and unadjusted p-values. A mean difference describes the contrast between group averages in the outcome’s measurement units. Standard deviations describe variation among individual observations within each group; they are not confidence intervals for the mean. General statistical explanation: if the outcome distribution is strongly skewed or contains influential observations, means and standard deviations may not fully represent its pattern. Distributional checks and transformations are not reported in the registry record.

What does over-dispersion mean for count data?

General statistical explanation: over-dispersion occurs when the variability in count data exceeds what a simple Poisson model expects. In such cases, a Poisson model can make standard errors too small and intervals too narrow unless the extra variability is addressed. The posted primary outcome is a binary abstinence outcome, not a count outcome, and the registry does not describe a count-data analysis for it. Over-dispersion is therefore not a basis for interpreting the primary comparison. The registry’s detailed modeling choices for secondary outcomes are not fully reported.

Randomization can support a causal comparison when allocation, follow-up, outcome ascertainment, and analysis are handled appropriately. The registry records randomized allocation but does not report the random sequence method, allocation concealment, missing-data handling, or analysis population. Those omissions limit how specifically the posted results can be linked to an intention-to-treat analysis or to a particular model.

11. Confidence Intervals and Precision

The primary risk-difference estimate is 0.206, and its confidence interval runs from 0.014 to 0.399. The interval is above the no-difference value of 0, which is consistent with the unadjusted p-value of 0.04 under common two-sided testing conventions. The registry does not state the confidence level or the exact method used to construct this interval, so those details should not be assumed.

The interval is also wide relative to its lower bound: the plausible values under the interval procedure range from a small positive contrast to a much larger one. That breadth matters because the point estimate alone can give a false impression of precision. The observed direction is clear in the posted arm values, but the size of the underlying contrast is less certain. A confidence interval is not a range containing a fixed proportion of individual participant outcomes, and it is not a probability statement about where the true effect lies.

The risk ratio estimate is 3.2, with an interval from 0.956 to 10.71; the odds ratio estimate is 4.143, with an interval from 0.999 to 17.18. Both intervals span a broad range of relative effects. In particular, their lower limits are close to the ratio value representing no difference. The interval for the odds ratio reaches 0.999, and the interval for the risk ratio begins at 0.956. These relative summaries therefore carry substantial uncertainty despite point estimates above the no-difference value.

The group sizes reported for the primary outcome are 32 in the placebo arm and 30 in the D-cycloserine arm. With limited information from each group, the estimate can be sensitive to a small number of outcome classifications. The registry does not report missing outcome counts, participant-level data, or sensitivity analyses, so the effect of incomplete follow-up or different abstinence rules cannot be assessed from the posted record.

12. 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 planning illustrations are expressed as participants per arm for the binary and continuous outcomes discussed in the record. They are not total event counts. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each illustration uses a stated fraction of the observed effect as the effect to detect. The trial’s own original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the estimated number of participants per arm under which the planning calculation would have an 80% chance of detecting the selected effect, if that effect and the stated assumptions held. The 90% power column gives the corresponding planning number for a 90% chance. These are design calculations, not guarantees that a study of that size will find a statistically significant result. The selected effect is based on the observed effect, and the observed estimate may differ from the effect in a future study.

The planning rows describe calculations for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. Smaller effects require more participants per arm to achieve the same target power under the stated assumptions. This illustrates why planning around a smaller, more cautious effect can imply substantially greater recruitment needs than planning around the full observed contrast.

These figures are not observed power. Observed power is not a useful substitute for reading the effect estimate and its confidence interval: once the data are collected, uncertainty is better understood from the estimate, interval, and the study’s analysis details. The planning values are illustrations based on observed results, not evidence that the completed trial was designed with these assumptions or had a particular power before it began.

13. 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 = 0.094; treatment proportion p₁ = 0.300; average p̄ = 0.197.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5623 = 1.1022.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5431 = 0.4571.
4. n = (1.1022 + 0.4571)² / (0.2062)² = 57.2, rounded up to 58 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 <- 0.09375                          # control proportion
p1 <- 0.3                          # 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(1399866)
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 = 58 (80% power), 77 (90% power)
 75% of observed effect: n per arm = 92 (80% power), 123 (90% power)
 50% of observed effect: n per arm = 183 (80% power), 244 (90% power)
power.prop.test: 57.2 
Simulated power at n = 58 per arm: 0.831 (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.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and multiple secondary outcomes, including five named secondary measures and six total outcome measures. It posts numerical results for three secondary outcomes and gives two ANOVA p-values for skin conductance. The record does not report a prespecified hierarchy among outcomes, a multiplicity adjustment, or which analyses were designated confirmatory. Without that information, the unadjusted p-values should not be treated as if they account for all outcome and analysis opportunities.

Multiplicity is relevant because testing several outcomes can increase the chance of a nominally small p-value arising by chance. General statistical explanation: procedures such as adjusting a significance threshold or controlling a family-wise error rate can address this issue, but the appropriate method depends on which tests form the planned family and what inferential claims are intended. The registry record does not report whether any such procedure was planned or used. The posted p-values are therefore best read as unadjusted results rather than evidence that multiplicity has been controlled.

The registry does not report whether primary analyses used an intention-to-treat population, a per-protocol population, or another analysis set. It also does not give numbers with missing primary outcomes, reasons for missingness, or methods used to handle missing data. These omissions matter for an abstinence outcome because the endpoint’s meaning depends on how participants with incomplete follow-up are classified and whether participants are analyzed in their randomized groups.

The record does not report the trial’s complete statistical analysis plan, interim analyses, stopping rules, or handling of protocol deviations. The details of random sequence generation and allocation concealment are also not reported in the registry record. Triple masking and randomized allocation are stated design features, but those labels do not supply the missing operational details. As a result, the extent to which the posted comparison followed a prespecified inferential plan cannot be established from the registry record.

15. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: compression fracture (3.1%).

The posted serious adverse event figures show 1 affected participant among 32 at risk in the placebo group and 0 among 30 at risk in the D-cycloserine group. The record lists compression fracture as a top serious adverse event term at 3.1%. It does not establish whether that term corresponds to the reported event in a particular arm, nor does it report a causal relationship between study medication and the event.

Other adverse events are reported for 24 of 32 participants in the placebo group and 24 of 30 in the D-cycloserine group. These are participant counts, not descriptions of event severity, duration, or recurrence. The registry does not provide a detailed breakdown of other adverse-event types or explain how events were collected and coded.

Deaths are listed as null for both groups. This means death counts are not reported in the posted safety entry; it should not be read as a documented count of zero. The small group sizes and limited safety detail mean the listed figures describe what the registry reports, not a comprehensive characterization of comparative safety or causation.

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

The posted primary summaries show a higher continuous-abstinence percentage in the D-cycloserine group than in the placebo group, with a risk difference of 0.206 and a confidence interval from 0.014 to 0.399. The unadjusted p-value is 0.04. This describes the observed contrast among the posted outcome groups and indicates that, under the comparison’s statistical assumptions, the data are not centered on an estimated risk difference of 0. The interval nevertheless allows a range of effect sizes, so the result is more informative about direction than about the exact magnitude.

The finding applies to D-cycloserine added to cue-exposure treatment in the trial’s selected participants. It does not show the effect of D-cycloserine without cue-exposure treatment, does not compare cue-exposure treatment with no cue-exposure treatment, and does not isolate the prior nicotine replacement therapy or varenicline. The registry does not report enough detail to extend the result to populations with different eligibility, abstinence, or treatment conditions.

The result does not establish that every participant assigned to D-cycloserine maintained abstinence, or that the same group contrast would occur in another study. The interval estimates uncertainty around a group-level contrast, not individual outcomes. The registry does not report outcome missingness, endpoint adjudication rules, or a primary analysis population, all of which affect how the result should be interpreted.

The secondary measures do not provide a clear, consistent explanation for the primary result, and some listed secondary outcomes lack posted numerical results. The safety record includes serious and other adverse-event counts but does not give enough information to determine causation or comprehensively compare event patterns. Overall, the posted registry results describe a potentially important observed contrast with uncertainty and reporting limitations; they do not, on their own, justify a medical recommendation or a broad claim about treatment effectiveness.

17. Why This Trial Matters Statistically

This trial is statistically notable because its primary outcome is directly expressed as abstinence, while the comparison is an add-on contrast: D-cycloserine plus cue-exposure treatment versus placebo plus cue-exposure treatment. That distinction defines what the observed risk difference can address. Clear interpretation depends on keeping the treatment contrast separate from the broader smoking-cessation program that participants received.

The primary point estimate and its uncertainty tell different parts of the story. The risk-difference estimate is 0.206, while the interval from 0.014 to 0.399 spans a broad range of positive contrasts. The relative measures also have wide intervals. This is a useful example of why the point estimate, confidence interval, and unadjusted p-value should be read together rather than treating a threshold-crossing p-value as a complete account of evidence.

The record also illustrates the importance of transparent reporting. It identifies randomization and triple masking, but does not report allocation procedures, the full analysis plan, missing-data handling, or multiplicity methods. It lists an enrollment figure of 150 while the study summary describes a plan to enroll 175 eligible participants with an aim of randomizing 60. Posted outcome groups contain 32 and 30 participants, but the registry does not explain how these counts relate to the different enrollment descriptions. These details matter for assessing design, analysis, and the flow from planned recruitment to analyzed outcomes.

Finally, the planning illustrations show how power calculations depend on the effect size selected. The observed effect is only one possible basis for planning, and smaller target effects require larger participant numbers under the stated assumptions. The illustrations are not evidence of the original design’s justification or of observed power. This combination of effect estimation, uncertainty, design context, and reporting gaps makes the trial useful for careful statistical reading.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The primary outcome details are incomplete in the registry record. It names self-report and saliva cotinine as measurement sources and gives a timeframe of up to 6 weeks, but does not report the exact continuous-abstinence definition, the rules for combining the two sources, or the handling of discordant assessments. It also does not clarify how the week 6 follow-up description relates to the listed timeframe.

The registry does not report the primary analysis population, missing outcome counts, missing-data methods, or sensitivity analyses. Without these details, the reader cannot determine whether all randomized participants were included or how incomplete follow-up influenced the posted abstinence summaries. The random sequence method and allocation concealment are also not reported, despite the registry identifying the study as randomized and triple masked.

There is an unexplained difference between the registry enrollment entry of 150 and the summary’s plan to enroll 175 eligible participants with an aim of randomizing 60. The primary outcome groups are reported as 32 and 30 participants, but the registry does not explain participant flow, exclusions, or the relation of the group counts to those planning figures. The summary also contains incomplete text about visit schedules, limiting a full reconstruction of the study procedures.

Secondary results are incomplete: numerical findings are posted for three outcomes, while craving and attentional-bias results are not reported in the registry record. The record does not describe multiplicity control or fully specify the statistical models, including the two listed skin-conductance ANOVA tests. Safety reporting gives aggregate counts and a top serious-event term but does not include event-level detail or causal assessments. These reporting limitations constrain interpretation of the result’s precision, robustness, and scope.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Cognitive Remediation With D-Cycloserine — NCT01399866.
• Registry record last updated 2018-09-26; status last verified 2018-08.
• Results first posted 2015-05-04.
• 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.

22. Record Summary

NCT01399866 is a completed phase 3 randomized, triple-masked, parallel-group study titled “Cognitive Remediation With D-Cycloserine.” It compares D-cycloserine plus cue-exposure treatment with placebo plus cue-exposure treatment. The medication descriptions specify 50 mg oral capsules, given as a single dose twice, one week apart. The primary outcome is continuous abstinence from tobacco smoking, assessed using self-report and saliva cotinine, with a timeframe of up to 6 weeks.

The posted primary arm summaries are 9.0 for placebo and 30.0 for D-cycloserine, with group sizes of 32 and 30. The risk-difference estimate is 0.206, with a confidence interval from 0.014 to 0.399 and an unadjusted p-value of 0.04. Secondary numerical results are posted for three outcomes, with additional listed outcomes lacking numerical results in the registry record. The record does not report a complete analysis plan, missing-data methods, or multiplicity procedures.