Effect of Quetiapine on Marijuana Withdrawal and Relapse: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Quetiapine on Marijuana Withdrawal and Relapse (NCT00743366), a randomized phase 2 study. The primary outcome is Measure of Relapse: Change in Puffs Chosen Between Baseline and Relapse Phase.

2. Clinical Question

3. Trial Design

The registry identifies this as a phase 2, randomized, double-masked crossover study of quetiapine and marijuana. Its status is completed. The recorded study start is 2008-08, and primary completion is recorded as 2009-03. The registry lists enrollment of 20 and names New York State Psychiatric Institute as the sponsor.

A crossover design means that participants receive more than one study condition at different times, rather than being assigned only to a single condition for the entire study. This design can allow comparisons within participants, but interpretation depends on details such as treatment sequence, the timing of periods, and whether effects from an earlier period could carry into a later period. Those details are not reported in the registry record in the information available for this outcome. The record’s arm descriptions name quetiapine with marijuana and placebo with marijuana; they do not fully explain the crossover sequence or the participant flow through each condition.

The quetiapine arm description states a dose of 200 mg/day, with study capsules administered twice per day. The placebo arm description identifies placebo capsules. Marijuana is listed as an intervention in both arms, and the arm labels include marijuana concentrations of 6.2% and 0.0%. The registry describes the study objective as investigating the interaction between marijuana and quetiapine, with the goal of informing marijuana treatment outcome.

For the primary outcome, the registry reports 14 participants in each of the two outcome groups. Because the study is crossover, these group entries should not automatically be interpreted as separate sets of participants. The registry does not report how the outcome entries relate to enrollment, whether all participants contributed data under both conditions, or why the outcome group entries have their reported sizes.

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: 14 volunteers completed the study (12 males; 2 females). An additional 6 volunteers enrolled (5 males, 1 female), but did not complete.

Intervention 1 (8 Days)

Reasons for not completing this period:

Intervention 2 (8 Days)

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 Measure of Relapse: Change in Puffs Chosen Between Baseline and Relapse Phase, measured over Days 1-3 (Baseline) and Days 6-8 (Relapse Phase).

The primary endpoint is titled “Measure of Relapse: Change in Puffs Chosen Between Baseline and Relapse Phase.” It measures marijuana self-administration through the number of puffs chosen. The registry explains that each initial puff costs $10 and is described as a burden to overcome before smoking. The measure is therefore intended to capture a behavioral choice related to self-administration and relapse, rather than a direct clinical symptom score.

The endpoint compares the baseline period, Days 1-3, with the relapse phase, Days 6-8. In each three-day period, the puffs chosen by each participant are averaged to produce a single value. The outcome is continuous, and the registry reports group means with standard errors. The posted values are 2.5 for quetiapine with marijuana and 1.5 for placebo with marijuana.

The endpoint is used to quantify change in the recorded behavior between the two phases. The registry does not report further details about how the change was calculated for each participant, how missing daily observations were handled, or whether the endpoint was analyzed using a model that accounts for the crossover structure. Those details matter when judging how closely the posted group comparison reflects the study’s intended within-participant comparison.

7. Results Posted in the Registry

• Quetiapine, Marijuana: mean 2.50 versus 1.50 on control; difference 1.00 (95% CI -1.46 to 3.46), standardized effect d = 0.30; z-test p = 0.425.

8. Statistical Interpretation

9. Statistical Methods Explained

The reported outcome is continuous, so the registry presents group means and standard errors, followed by a mean difference and an interval. The comparison is an unadjusted re-calculation from the posted summary statistics. It should be distinguished from a fully described analysis conducted by the study sponsor, because the registry does not report the analysis model or its assumptions for this endpoint.

What does the mean difference represent?

A mean is a measure of the center of a set of observations. The posted mean for quetiapine with marijuana is 2.5, while the posted mean for placebo with marijuana is 1.5. The reported mean difference of 1.0 is the quetiapine-group mean minus the placebo-group mean. A positive value indicates that the first group’s reported mean is higher. It does not, on its own, identify why the groups differ or show that the intervention caused the difference.

The endpoint is described as change between baseline and relapse phase, with each participant’s puffs chosen averaged over each three-day period. The group summaries do not show individual participant values or how those paired phase measurements were handled. In a crossover trial, the same participant may contribute observations under different treatment conditions. Those measurements can be correlated. A method that accounts for within-participant correlation can yield different uncertainty estimates from a method that treats the groups as independent. The registry does not report whether the recalculated group comparison accounts for this feature.

What do the standard errors describe?

The registry gives standard errors of 0.6 for the quetiapine group mean and 1.1 for the placebo group mean. A standard error describes the statistical uncertainty of an estimated mean, rather than the spread of individual participant outcomes. It is affected by variability in the observations and the amount of information contributing to the estimate. The registry does not provide the raw outcome data, so the distribution and participant-level variability cannot be inspected from these summaries alone.

For context, a pooled standard deviation of 3.315 appears in the recalculated comparison. A standard deviation describes variation among observations, whereas a standard error describes uncertainty in an estimated mean. These quantities answer different questions. Neither summary reveals whether the outcome distribution is symmetric, has outliers, or contains many repeated values. Those features can matter for a continuous outcome, particularly when the recorded outcome is a count of puffs.

How should the interval be read?

The interval for the mean difference runs from -1.456 to 3.456. In general, a confidence interval expresses uncertainty around an estimate using a method that has a stated coverage level under its assumptions. Here, the registry information does not state the confidence level or document the method used for the interval, so the interval should be interpreted as the posted uncertainty range without assigning it an unreported level. Its inclusion of zero indicates that a zero difference is among the values not excluded by this interval.

Intervals also show uncertainty in directions not captured by the point estimate alone. The estimate is 1.0, but the interval extends into negative values and into positive values. The data summarized by the interval therefore do not pin down the direction or size of a difference precisely. The interval does not tell whether any value within it is clinically important; that judgment would require a prespecified meaningful difference, which is not reported in the registry record.

What does the p-value add?

The unadjusted p-value is 0.425. A p-value is calculated under a null hypothesis and a statistical model. In general, it measures how incompatible the observed data, or more extreme data, are with that null model. It is not the probability that the null hypothesis is true, and it is not a measure of the probability that the result occurred “by chance.” The registry does not report the full model and testing procedure behind a sponsor analysis, so the posted p-value should be understood as the unadjusted value attached to the summary-statistic comparison.

A p-value alone does not show the magnitude or precision of a difference. The mean difference and its interval provide complementary information. Nor does a p-value above a conventional threshold establish equivalence or no effect. Establishing equivalence would require a defined equivalence margin and an analysis designed to address it; such a margin or analysis is not reported in the registry record.

Why does crossover structure matter?

In general, crossover analyses may need to account for treatment, period, sequence, and repeated measurements within participants. Carryover is a possible concern when effects from one treatment period persist into another. The registry identifies the study as crossover but does not report the sequence allocation, period structure, washout details, carryover assessment, or model specification for the primary endpoint. This absence prevents readers from verifying whether the posted comparison reflects the planned within-participant design.

These limitations do not invalidate the arithmetic of the reported summary-statistic re-calculation, but they limit what can be inferred from it. In particular, the calculation should not be treated as a replacement for a prespecified crossover model or the sponsor’s own analysis. The registry record reports no analysis entries for the outcome, and no adjusted or model-based primary comparison is described. The numerical summaries are therefore useful for describing the posted group results and their uncertainty, while leaving important questions about the analysis unresolved.

10. Confidence Intervals and Precision

The estimated unadjusted mean difference is 1.0 puff, with an interval from -1.456 to 3.456. The interval spans zero and includes values on both sides of it. This means the posted data do not locate the difference precisely enough to rule out a range of directions and magnitudes under the interval’s calculation. The registry does not state the confidence level or the method used to form the interval, so neither should be inferred from the record.

The group means are 2.5 for quetiapine with marijuana and 1.5 for placebo with marijuana. Their standard errors are 0.6 and 1.1, respectively. Standard errors describe uncertainty around the group means, not the range of individual outcomes. The registry does not provide raw observations, participant-level change scores, or a distribution plot from which to assess variation, skewness, or influential observations.

Precision also depends on the analysis structure. Because this is a crossover study, the relationship between measurements from the same participant can affect uncertainty. The registry does not report whether this relationship was incorporated into the outcome comparison. The reported outcome entries list 14 participants per group, but the record does not explain how those entries correspond to participants who may have experienced more than one condition.

The interval’s breadth and the missing crossover analysis details mean that the point estimate should not be treated as a precise estimate of a causal effect. The interval describes uncertainty in the posted comparison, not uncertainty arising from every possible source of bias or design limitation.

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 the observed effect, rather than the original design assumptions for the trial. They are expressed as participants per arm for 80% power and participants per arm for 90% power; 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. The effect to detect is set to the stated fraction of the observed effect.

In general, power is the probability that a specified analysis will reject its null hypothesis when a particular effect is assumed to be true. The 80% power column gives the planned number of participants per arm under which the calculation targets 80% power for the chosen effect and assumptions. The 90% power column gives the corresponding planning target for 90% power. These are prospective planning quantities, not a description of what happened in the completed study. This is not observed power.

For planning around 100% of the observed effect, the figures are 173 participants per arm for 80% power and 231 participants per arm for 90% power. For planning around 75% of the observed effect, they are 307 and 411 participants per arm, respectively. For planning around 50% of the observed effect, they are 691 and 924 participants per arm, respectively. Smaller effects need more participants to reach the same target power under these assumptions.

These values are illustrative and depend on the assumptions listed in the registry. They do not establish what sample size the investigators originally planned or whether the original study met its design goals. The original sample-size justification and design assumptions are not reported in the registry record. The planning figures also should not be read as a revised estimate of treatment efficacy or as an assessment of the probability that the observed result is true.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 1.000; pooled standard deviation σ = 3.315.
2. n = 2 × (1.96 + 0.842)² × 3.315² / 1.000² = 172.5, rounded up to 173 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
delta <- 1                      # observed difference in means
sigma <- 3.31511689085016                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(743366)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 173 (80% power), 231 (90% power)
 75% of observed effect: n per arm = 307 (80% power), 411 (90% power)
 50% of observed effect: n per arm = 691 (80% power), 924 (90% power)
power.t.test: 173.5 
Simulated power at n = 173 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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 registry lists one primary outcome measure and no posted secondary outcome measures. It also lists no analysis entries for the outcome. The available record does not report a prespecified statistical analysis plan, the order in which outcomes were tested, or whether any multiplicity adjustment was planned or applied. Without those details, it is not possible to determine how the primary comparison fits into the full set of analyses that may have been considered.

Multiplicity arises when multiple outcomes, time points, treatment contrasts, or subgroup comparisons are tested. In general, testing many hypotheses can increase the chance of obtaining a nominally unusual result even when no underlying effect is present. Methods such as adjustment procedures or a prespecified testing hierarchy can address that issue, but the registry does not report whether any such approach was used. No adjustment should be assumed from the posted unadjusted p-value.

The registry also does not describe the analysis population for the primary endpoint. It does not state whether the outcome analysis included all randomized participants, only participants with complete observations, or another defined group. The outcome entries report 14 participants in each group, while enrollment is listed as 20. In a crossover study, group entries can reflect observations under conditions rather than mutually exclusive groups of participants. The record does not explain the relationship among enrollment, treatment exposure, and the endpoint entries, so attrition or exclusions cannot be inferred from those figures.

Missing-data handling is not reported in the registry record. There is no description of how missing baseline or relapse-period observations were addressed, whether partial three-day periods were included, or whether any imputation or sensitivity analysis was performed. These omissions matter because complete-case analyses and other approaches can rely on different assumptions about why data are missing.

Further crossover-specific analysis details are also not reported, including treatment sequence, period effects, within-participant correlation, and carryover assessment. The record does not say whether those factors were accounted for in a model. Consequently, the unadjusted summary-statistic comparison should be read as a limited description rather than as a full account of the trial’s planned or sponsor-conducted inference.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse event figures for two groups labeled “Quetiapine (200mg/Day), Placebo” and “Placebo, Quetiapine (200mg/Day).” Each group lists 20 participants at risk for serious adverse events and zero serious events. These are the posted serious-event counts for the labeled groups; the record does not explain how the groups correspond to the crossover periods or to the primary outcome entries.

The record lists other adverse events in 2 participants in the quetiapine-then-placebo group and 1 participant in the placebo-then-quetiapine group, with 20 participants at risk in each group. The categories or descriptions of those other events are not included in the available adverse-event details. The registry does not report a death count for either group, so deaths are not reported in the registry record. No serious adverse event terms are listed.

These figures are counts as recorded, not a complete comparison of safety. They do not describe event severity beyond the serious-versus-other categorization, timing, duration, causality assessment, or whether a person had more than one event. Because the study is crossover, the group labels should not be interpreted as proof that the groups contain different participants. The registry record does not provide enough information to characterize event rates across treatment periods or to establish comparative safety.

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

The registry’s primary outcome is a behavioral measure: change in the average number of marijuana puffs chosen between the baseline phase and the relapse phase. The posted mean is 2.5 in the quetiapine-with-marijuana group and 1.5 in the placebo-with-marijuana group. The unadjusted mean difference is 1.0, with an interval from -1.456 to 3.456 and an unadjusted p-value of 0.425. These values describe the outcome comparison recorded in the registry.

The results do not establish that quetiapine caused the higher reported mean, nor do they establish that the conditions were equivalent. The interval includes zero and extends in both directions, leaving uncertainty about the direction and size of a difference. The registry does not report a clinically meaningful threshold for this endpoint, so the practical importance of any possible difference cannot be determined from the statistical summaries alone.

The study’s crossover design could support within-participant comparisons, but the registry does not describe how the primary outcome was analyzed in relation to treatment periods, sequence, or possible carryover. The unadjusted comparison from summary statistics is not evidence that those features were addressed. The registry also does not report participant-level observations or missing-data methods, which limits assessment of the outcome calculation and its robustness.

The serious adverse event figures record zero serious events in each labeled group, while other adverse events are reported for 2 participants in one group and 1 in the other. These counts do not provide a full safety profile: event descriptions, timing, and causality are not reported in the available record. The figures should be read as registry counts rather than as a definitive comparative safety analysis.

In short, the posted results show a positive unadjusted difference, but its uncertainty is substantial and important design and analysis details are missing. The record alone cannot support a conclusion about treatment benefit, lack of benefit, equivalence, or comparative safety.

16. Why This Trial Matters Statistically

This trial is statistically interesting because it combines a crossover design with a behavioral endpoint based on repeated choices. A crossover can make within-participant comparisons informative, since each participant may contribute observations under multiple conditions. That advantage depends on an analysis that respects the repeated nature of the data and handles treatment sequence and period structure appropriately. The registry identifies the crossover design but does not report the details needed to verify how those features entered the primary analysis.

The outcome also illustrates the distinction between a point estimate and its precision. The mean difference is 1.0 puff, while the interval runs from -1.456 to 3.456. The estimate alone can look directional, but the interval conveys that the data are compatible with a range that includes zero and effects in either direction. Statistical interpretation should attend to both the estimated difference and its uncertainty, rather than reducing the result to a single p-value.

The registry’s endpoint averages behavior over three-day periods, and each initial puff is described as carrying a $10 cost. That context explains why the measure was chosen as a behavioral indicator, but it does not make the outcome a direct measure of clinical benefit. The record does not report a threshold for a meaningful change or an analysis linking this measure to a later clinical outcome.

Finally, the mismatch between the listed enrollment and the primary outcome group entries underscores the importance of reporting participant flow and analysis populations, especially in crossover trials. The registry does not explain how those entries map to participants or periods. This limits independent assessment of the comparison and demonstrates why transparent reporting of model structure, missing data, and analysis populations is essential for interpreting trial statistics.

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.

Several trial-specific limitations affect interpretation. Although the registry identifies a randomized, double-masked crossover design, it does not report the treatment sequence, period structure, washout details, or assessment of carryover. These omissions are important because a crossover comparison can depend on the order and timing of treatment exposure, as well as on within-participant correlation.

The primary outcome entries list 14 participants per group, while the registry lists enrollment of 20. The record does not explain whether the group entries represent participants, condition-specific observations, or another analysis set. Because the study is crossover, the entries should not be treated as independent groups of people without further information. Participant flow, exclusions, and reasons for unavailable outcome data are not reported.

The registry provides group means and standard errors but not participant-level outcomes, distributions, or complete details of the calculation of change. It does not report the model used for the sponsor’s primary analysis, how repeated observations were handled, or whether the comparison was adjusted for period or sequence. The posted unadjusted re-calculation therefore cannot resolve those design and model questions.

Missing-data procedures and sensitivity analyses are not reported. Neither a clinically meaningful threshold for the endpoint nor the original sample-size justification is reported in the registry record. The record also contains no posted secondary outcome measures or analysis entries, limiting assessment of the broader analysis plan. These are reporting limitations; the available information does not establish whether particular procedures were or were not used outside the registry record.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Effect of Quetiapine on Marijuana Withdrawal and Relapse — NCT00743366.
• Registry record last updated 2017-08-18; status last verified 2017-07.
• Results first posted 2017-07-12.
• 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

The registry describes a completed phase 2 randomized, double-masked crossover study sponsored by New York State Psychiatric Institute, with enrollment of 20. The recorded start is 2008-08 and primary completion is 2009-03. The study concerns marijuana smoking and examines quetiapine with marijuana against placebo with marijuana.

The primary endpoint measures change in average puffs chosen from baseline, Days 1-3, to the relapse phase, Days 6-8. The posted group means are 2.5 and 1.5, with an unadjusted mean difference of 1.0 and an interval from -1.456 to 3.456; the unadjusted p-value is 0.425. The registry reports zero serious adverse events in each labeled safety group, with other adverse events recorded for 2 and 1 participants.

The registry does not report the detailed crossover analysis, missing-data procedures, analysis populations, or original sample-size assumptions. The outcome comparison should therefore be interpreted as a limited summary of the posted results.