Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder (NCT00156715), a non-randomized phase 4 study. The primary outcome is Mean Number of Drinking Days Per Week.

2. Clinical Question

3. Trial Design

This is a Phase 4, completed, non-randomized, unmasked, single-group study sponsored by Dartmouth-Hitchcock Medical Center. The record lists enrollment of 23. All participants were assigned to the quetiapine group; no control arm or randomized treatment allocation is listed. Without a concurrent comparison group, changes observed during treatment cannot by themselves separate treatment-associated change from other influences, such as changes over time or events occurring during follow-up.

The treatment description says quetiapine was initiated after informed consent and baseline measures, with titration toward a target dose of 600 mg in divided daily doses over two weeks. The previous antipsychotic medication was slowly tapered and discontinued. The remainder of the intervention description is not reported in the registry record. The study began in 2004-03, had primary completion in 2006-09, and is listed as completed.

The primary outcome was the mean number of drinking days per week, assessed using the Timeline Follow-back procedure. The record describes screening and baseline assessments and weekly assessments during the study. The primary analysis included only participants who received at least 4 weeks of quetiapine treatment. Because of site differences, it included only 11 participants from Site 1. The record notes that Site 2 participants were admitted directly from the hospital but does not report the rest of that explanation.

Clinical symptoms are listed as a secondary outcome. The registry lists 2 outcome measures, but no analysis results are reported for the primary endpoint in the record. The statistical analysis plan, including any model or method used to evaluate change, 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: Prior to starting quetiapine, all participants first completed a screening assessment to establish diagnosis, amount of alcohol (and other drugs) consumed, and current medications and medical status. This data was used to characterize the group and assess whether they met eligibility criteria for the study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Only those participants who received at least 4 weeks of treatment with quetiapine were included in this analysis. Site differences resulted in only the 11 participants from Site 1 to be included in the analysis. Participants from Site 2 were all admitted to the study directly from the hospital which could have affected their alcohol consumption.

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 Mean Number of Drinking Days Per Week, measured over 12 Weeks.

The primary endpoint is the mean number of drinking days per week, with a timeframe of 12 weeks. It is a continuous outcome: each participant’s drinking days are represented numerically, and a group mean describes the average level for the analyzed participants. A lower mean at a later assessment could represent fewer drinking days on average, but the registry record does not report the outcome values or the direction or size of any observed change.

The Timeline Follow-back procedure was used to assess alcohol and other substance use. The description says participants used a calendar to report alcohol and other drug use since the last visit. It was used at screening and baseline to establish current use and weekly during the study to assess continued use. At screening, the assessment covered the four weeks before the visit. This type of repeated self-report can provide information about use over time rather than relying on a single recollection of overall behavior.

The endpoint is relevant to the stated research question because drinking days per week directly reflects the frequency of alcohol use. It does not, by itself, describe quantities consumed, consequences of use, or other substances separately. The registry record does not report a primary endpoint estimate, standard deviation, confidence interval, or statistical test result. Consequently, the recorded endpoint definition can be described, but its observed pattern and precision cannot be evaluated from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean describe? A mean is the arithmetic average of values in an analyzed group. For this endpoint, the values represent drinking days per week. A mean is useful for describing the overall level of a continuous outcome, but it does not show how individual participants’ values are distributed. Participants can differ substantially even when the group mean is similar. The registry identifies the measure as a mean and the dispersion measure as a standard deviation, but it does not report either numerical result.

What does a standard deviation add? In general, a standard deviation describes the spread of individual observations around their mean. A small spread indicates that observations tend to lie closer to the mean; a larger spread indicates more variability. It is not the same as a confidence interval, and it does not by itself quantify the precision of an estimated mean. Since the registry record does not provide a standard deviation for the primary outcome, the degree of participant-to-participant variability cannot be assessed from the posted results.

Why are repeated assessments useful? The Timeline Follow-back procedure was used at screening, baseline, and weekly during the study. Repeated measurement can describe the course of an outcome over time and can help distinguish a single unusual assessment from a pattern across visits. The registry description says a calendar was used to prompt reports of alcohol and other drug use since the last visit; the screening assessment covered the four weeks before the visit. However, the record does not report how repeated observations were incorporated into an analysis, how missing weekly assessments were handled, or whether a particular visit or summary across visits defined the final endpoint result.

What would a confidence interval mean? In general, a confidence interval expresses the statistical uncertainty around an estimate. A narrower interval indicates greater precision under the assumptions of the method used; a wider interval indicates less precision. It does not show the range of outcomes for individual participants, nor does it by itself establish causation. No confidence interval for the primary endpoint is reported in the registry record, so precision cannot be judged from such an interval.

Why does the design affect interpretation? In a single-group study, an outcome measured during treatment can be compared with an earlier measure, but the change does not have a separate control group as a benchmark. General explanations for change include treatment, time, other interventions, changes in substance use circumstances, and variation in measurement. Random allocation and a concurrent comparator can reduce some sources of bias in a treatment comparison. Neither is listed for this study: the allocation is non-randomized, the model is single-group, and masking is absent. The record does not report a statistical model or test used for the primary endpoint.

How should planning calculations be understood? The sample-size planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They refer to detecting a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the study had a particular probability of detecting an effect. They also do not describe the trial’s actual design: the registry lists a single group rather than two equally allocated arms. The registry record does not report its own sample-size justification, and the observed primary effect needed to interpret the illustration is not reported there.

What can be concluded from the analysis record? The registry lists 2 outcome measures and 0 analyses. That does not provide a method for estimating change, handling repeated measures, or assessing uncertainty. Those statistical details are not reported in the registry record. Without the outcome estimate and its uncertainty, readers cannot assess whether any observed change was small or large relative to the spread of values, nor can they evaluate a statistical test or interval estimate.

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("QUET")
n   <- c(11)
m   <- c(2.7)
sp  <- c(2.3)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  QUET  11  2.700  2.300  1.155  4.245

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns arise when a study evaluates multiple outcomes, time points, or statistical comparisons. In general, examining many results can increase the chance that at least one appears notable by chance. A prespecified hierarchy or an adjustment for multiple comparisons may address this issue, but the registry record does not report whether either approach was planned or used. It lists 2 outcome measures, including clinical symptoms as a secondary outcome, and 0 analyses. No multiplicity strategy is reported in the registry record.

The outcome description reports screening, baseline, and weekly assessments, but it does not explain how measurements across visits were combined, which assessment was used for the primary comparison, or whether all scheduled assessments were analyzed. The statistical plan is not reported in the registry record. It is therefore not possible to determine whether the primary endpoint was analyzed as a change from baseline, as a series of repeated values, or using another approach.

Missing-data handling is also not reported. The analysis population was restricted to participants who received at least 4 weeks of quetiapine, and only 11 participants from Site 1 were included because of site differences. The record does not report how many otherwise eligible participants lacked outcome data, whether missing observations were imputed, or how participants with incomplete follow-up were treated. Such information matters because an analysis based on available observations can differ from one that accounts for incomplete follow-up in another way.

The primary analysis population is not described as an intention-to-treat population, and the registry record does not report a formal population definition beyond the treatment-duration and site criteria. It also does not report an interim-analysis plan or sample-size justification. These omissions limit assessment of the analysis process and the possibility of selective reporting.

12. 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: increased psychosis (12.5%), suicidal ideation/attempt (12.5%), pneumonia (6.2%), lump in breast (6.2%).

The registry lists 3 participants affected by serious adverse events among 16 at risk in the QUET group. For other adverse events, it lists 13 affected among 16 at risk. These are separate summary figures for the safety record; they do not show event timing, severity beyond the serious classification, duration, or whether an individual participant had more than one event. The registry record does not report deaths.

The listed serious-event terms include Increased Psychosis and Suicidal Ideation/Attempt, each reported as 12.5%, and Pneumonia and Lump in Breast, each reported as 6.2%. These percentages are registry entries for terms, not proof of a causal relationship with quetiapine. The record does not explain whether terms represent unique participants, how overlapping events were counted, or the basis for each percentage beyond the listed safety group.

Adverse-event summaries are descriptive. In general, an event occurring during a study does not by itself show that the study treatment caused it; causal assessment requires attention to timing, clinical context, comparison data, and other evidence. Because there was no comparator group, the safety figures cannot provide a controlled estimate of excess risk attributable to treatment. The registry record does not report further safety-analysis methods or event-level details.

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

The record establishes the study’s purpose and design: to examine whether quetiapine treatment was associated with reduced substance use in people with schizophrenia, using mean drinking days per week as the primary endpoint. It also identifies a 12-week timeframe and describes repeated use of the Timeline Follow-back procedure. These details explain what the investigators intended to measure, but they do not show what the measured outcome was.

The primary result is not reported in the registry record. Without the mean values or an estimate of change, it is not possible to say whether drinking days increased, decreased, or remained similar. Without a measure of statistical uncertainty, it is also not possible to judge the precision of any estimate. The stated hypothesis should not be read as evidence that the hypothesized decrease occurred.

The design limits causal interpretation independently of the missing result. This was a non-randomized, unmasked, single-group study without a concurrent comparator. In general, differences between baseline and later observations in such a study may be associated with treatment, but they may also reflect other changes or time-related variation. The design does not isolate a treatment effect in the way a suitable randomized comparison can.

The analysis population was limited to participants who received at least 4 weeks of treatment, with only 11 participants from Site 1 included because of site differences. This selection and the absent information about missing assessments limit understanding of how representative the analyzed group was of the enrolled population. The registry record does not report the primary analysis methods or a statistical plan that would clarify these issues.

The safety counts describe adverse events recorded in the registry, not proof of treatment causation. They also do not replace a comparative safety analysis. Overall, the posted information supports a description of the study question, design, outcome definition, and safety summaries, but not a conclusion about the primary outcome’s direction, size, or precision.

14. Why This Trial Matters Statistically

This study illustrates why outcome definitions and outcome findings must be kept distinct. The registry identifies a clinically relevant measure—mean drinking days per week—and describes the procedure used to assess alcohol and other drug use over time. Yet without a reported mean or change estimate, the endpoint definition alone cannot answer the research question. A clearly named outcome does not substitute for its observed result.

It also shows why the design is central to statistical interpretation. A single-group study can describe observations among participants receiving treatment, but it lacks a concurrent counterfactual comparison. Non-randomized allocation and absence of masking further mean that the record does not describe protections against selection or assessment effects through those design features. Statistical methods cannot, by themselves, make an uncontrolled comparison equivalent to a randomized one.

The distinction between enrollment and analysis population is important as well. The registry lists enrollment of 23, but the primary analysis was limited to participants who received at least 4 weeks of treatment and, because of site differences, only 11 participants from Site 1. The size and selection of the analysis population affect how broadly an estimate could be interpreted, while incomplete reporting prevents a full assessment of those effects.

Finally, planning illustrations should not be confused with evidence from the trial. The stated assumptions describe hypothetical sample-size planning for two arms, whereas the recorded study design has a single group. Such illustrations are not observed power and cannot resolve the absence of primary results. Together, these features make the registry a useful case for separating study intent, design, analysis population, and reported evidence.

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 primary endpoint estimate is not reported in the registry record. As a result, the principal research question cannot be evaluated from the posted results: direction, magnitude, and precision of any change in drinking days per week are unavailable. The record also does not report a confidence interval, p-value, or standard deviation for this endpoint.

The study has no concurrent comparator and is listed as non-randomized, unmasked, and single-group. Any observed change would therefore be difficult to attribute specifically to treatment. The registry record does not report an analysis method that could be assessed for assumptions or suitability, and it does not report an analysis plan, multiplicity approach, or interim-analysis plan.

The primary analysis included only participants who received at least 4 weeks of quetiapine, and site differences restricted the analysis to 11 participants from Site 1. The record notes that Site 2 participants were admitted directly from the hospital but gives no further explanation. The registry does not report how this restriction affected the analysis, how missing outcome observations were handled, or whether analyzed participants differed from those not included.

The outcome relies on self-reported substance use collected through the Timeline Follow-back procedure. The registry describes calendar-based recall and weekly assessment, but does not report information about validation, completeness of assessments, or procedures for checking reports. The primary endpoint concerns drinking days and does not, on its own, summarize amounts consumed or outcomes for other substances. The registry record also does not report detailed safety methods or event-level information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder — NCT00156715.
• Registry record last updated 2018-03-14; status last verified 2018-03.
• Results first posted 2010-12-21.
• 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 registry lists NCT00156715 as a completed Phase 4 study sponsored by Dartmouth-Hitchcock Medical Center. It enrolled 23 and used a non-randomized, unmasked, single-group design with quetiapine. The study began in 2004-03 and had primary completion in 2006-09.

The primary outcome was mean drinking days per week over 12 weeks, assessed using the Timeline Follow-back procedure. The primary analysis included only participants who received at least 4 weeks of treatment and was limited to 11 participants from Site 1 because of site differences. Clinical symptoms are listed as a secondary outcome. The registry record does not report the primary outcome result or the statistical analysis methods.

The safety record lists serious and other adverse-event summaries, including serious-event terms and percentages. These descriptions do not establish that events were caused by treatment. The registry record does not report deaths.