Quetiapine Extended Release (XR) in Bipolar Patients With Comorbid Generalized Anxiety Disorder (GAD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Quetiapine Extended Release (XR) in Bipolar Patients With Comorbid Generalized Anxiety Disorder (GAD) (NCT00671853), a randomized phase 3 study. The primary outcome is Change in the 17 Item Hamilton Rating Scale for Depression (HAM-D-17) Score.

2. Clinical Question

The trial’s stated primary objective was to test a hypothesis about Quetiapine XR in acute treatment of bipolar depression with comorbid generalized anxiety disorder, in patients with or without a substance use disorder. The secondary aim was to generate an effect-size estimate to inform a future large-scale collaborative study and to configure outcome measures for that work. Those stated aims distinguish the clinical comparison from the trial’s exploratory planning role: an estimate from a relatively limited registry sample may be useful for planning, but its uncertainty remains important when judging how precisely it describes the comparison.

3. Trial Design

The registry describes a randomized, triple-masked, parallel Phase 3 trial. Its status is completed, and the recorded enrollment is 120. The listed intervention arms are Quetiapine XR and placebo for Quetiapine XR. The record does not identify which specific parties were masked, so the meaning of “triple” masking beyond the registry’s label is not reported in the registry record.

The registry lists the study start as 2008-04 and primary completion as 2011-03. The primary endpoint timeframe is Week 0 to Week 8. These dates describe the registry record and do not establish the duration of each participant’s involvement or the timing of every assessment. Those details are not reported in the registry record.

The primary outcome is continuous: change in HAM-D-17 score. The posted group summaries include 46 participants in the Quetiapine XR arm and 45 in the placebo arm for that endpoint. These outcome counts are not the same thing as the recorded overall enrollment, and the record does not explain the difference. Reasons for absent endpoint observations, if any, are not reported in the registry record.

The posted secondary outcomes include depression response and remission, Clinical Global Impressions scores, quality of life, and anxiety scores. The record lists six outcome measures overall and five secondary outcomes posted in the results data, but only three secondary outcome results are included in the analyzed results available for this comparison. The remaining secondary endpoint results and their analyses are not reported in the registry record. No protocol details about randomization sequence generation, allocation concealment, treatment adherence, or analysis populations are 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: The study consent 120 subjects. However, 29 subjects were considered screening failures and were not randomized.

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 Change in the 17 Item Hamilton Rating Scale for Depression (HAM-D-17) Score, measured over Week 0 - Week 8.

The primary endpoint is change in the 17 Item Hamilton Rating Scale for Depression (HAM-D-17) score from Week 0 to Week 8. It is a continuous measure, reported as a mean change with a standard deviation for each arm. The score ranges from 0 to 57, and higher scores indicate more depression. A score of 0-7 is considered normal, according to the endpoint description.

Change scores express how the measured rating differed over the stated assessment period. A negative mean change represents a reduction in score; because higher scores indicate more depression, a reduction points in the direction of less depression on this scale. The comparison of mean changes between randomized arms is intended to describe the difference in average score change associated with assignment to the two study groups. It does not by itself describe every participant’s experience or establish why an observed change occurred.

A continuous endpoint can retain information about the amount of change across the score range, rather than reducing all outcomes to categories such as response or remission. That is a general statistical reason to analyze a scale score as a mean. The clinical meaning of a particular difference depends on context beyond the arithmetic, including the measurement properties of the scale and what change is important to patients. A threshold for a clinically important difference is not reported in the registry record.

7. Results Posted in the Registry

• Quetiapine XR: mean -9.91 versus -7.41 on control; difference -2.50 (95% CI -7.81 to 2.81), standardized effect d = -0.19; z-test p = 0.357.

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.

Response Rate (≥ 50% Improvement) on Hamilton Rating Scale for Depression (HAM-D-17)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Quetiapine XR: 26.1% (12/46) versus 24.4% (11/45) on control; risk difference 1.6 percentage points (95% CI -16.2 to 19.5), risk ratio 1.07 (0.53–2.17); unadjusted two-proportion z-test p = 0.857.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Quetiapine XR and the control. The interval gives the range of effects that remain compatible with the data.

Remission Rate (≤ 7) on Hamilton Rating Scale for Depression (HAM-D-17)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Quetiapine XR: 13.0% (6/46) versus 13.3% (6/45) on control; risk difference -0.3 percentage points (95% CI -14.2 to 13.6), risk ratio 0.98 (0.34–2.81); unadjusted two-proportion z-test p = 0.967.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Quetiapine XR and the control. The interval gives the range of effects that remain compatible with the data.

Change in Clinical Global Impressions of Improvement or Severity (CGI-I or S) Score

• 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:
  • Quetiapine XR: mean -1.10 versus -0.80 on control; difference -0.30 (95% CI -0.79 to 0.19), standardized effect d = -0.25; z-test p = 0.227.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Quetiapine XR and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary results cover depression response, depression remission, and change in Clinical Global Impressions. The registry also lists quality of life and anxiety outcomes, but results for those measures are not reported in the registry record. Across the reported secondary outcomes, the observed group contrasts are small relative to their uncertainty: the response and remission comparisons have intervals that include no difference, and the Clinical Global Impressions mean-difference interval also includes zero. This broad pattern does not provide a clear secondary signal that resolves the uncertainty in the primary comparison.

These outcomes relate to the primary result by measuring different aspects of symptoms and status over the same Week 0 to Week 8 timeframe. The HAM-D-17 primary outcome compares average score change. Response and remission instead classify participants according to thresholds on that scale; Clinical Global Impressions captures a separate rating. Agreement across different measures could add context, while disagreement could reflect differences in the constructs or in the way continuous scores are categorized. The posted results do not support treating any one secondary measure as a replacement for the primary endpoint.

The secondary findings carry less inferential weight than a prespecified primary analysis. They are unadjusted, and the registry does not report a multiplicity procedure, a hierarchy of secondary hypotheses, or sponsor-reported analyses. Looking across multiple outcomes increases the possibility of chance findings. Accordingly, these results are best considered descriptive or exploratory rather than as independent confirmation of the primary comparison.

The registry’s secondary aim included generating effect-size estimates to plan future research. In that context, secondary outcomes may help identify measures worth considering, but estimates from this record remain uncertain. Results for the posted quality-of-life and anxiety measures, along with further analysis details, are not reported in the registry record. No conclusion about their pattern can be drawn from their absence.

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

• Response Rate (≥ 50% Improvement) on Hamilton Rating Scale for Depression (HAM-D-17)
• Remission Rate (≤ 7) on Hamilton Rating Scale for Depression (HAM-D-17)
• Change in Clinical Global Impressions of Improvement or Severity (CGI-I or S) Score
• Change in the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Score
• Change in Hamilton Rating Scale for Anxiety (HAM-A)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a continuous score, so the comparison is expressed as a difference between group means. A mean summarizes the average change in each arm, while the standard deviation describes how spread out individual changes are around that group average. The standard deviation is not the same as the uncertainty in the mean: uncertainty in a group mean also depends on the amount of information available. This distinction is useful when reading the reported group summaries and the interval for the between-arm difference.

The mean difference is defined by subtracting the placebo-arm mean change from the Quetiapine XR-arm mean change. With this ordering, a negative estimate indicates a more negative average change in the Quetiapine XR arm. Since higher HAM-D-17 scores indicate more depression, more negative change corresponds to a greater average reduction in the score. This is a direction-of-scale interpretation, not a claim about clinical benefit.

A confidence interval gives a range of estimates compatible with the observed data under the statistical procedure used. In repeated use of a procedure, intervals constructed in this way would cover the underlying parameter at the procedure’s stated coverage rate. The registry results do not state the confidence level for the posted interval, so no specific coverage percentage is assigned. An interval that crosses zero leaves both negative and positive differences among the values compatible with the data. Interval width conveys precision: a wider interval allows a broader range of possible differences.

The unadjusted p value is tied to a test of a null hypothesis of no difference in average change. In general, a smaller p value indicates that the observed data would be less compatible with that null model under the test assumptions. It does not quantify the chance that the null is true, and it does not tell whether an effect is important in practice. The registry gives an unadjusted p value of 0.357 for the primary mean comparison. No adjustment for multiple outcomes is reported for this value.

The use of “unadjusted” matters because the registry does not report a model adjusting for baseline scores or other participant characteristics. A simple comparison based on posted summaries does not account for potential covariates. Randomization is intended to support a fair comparison of assigned groups, but the registry record does not provide details of the randomization procedure or a prespecified analysis plan. The simple recalculation should therefore be read as a summary-based comparison, not as a substitute for a protocol-defined sponsor analysis.

Why use a continuous score?

A continuous score records gradations in severity and change. Comparing means can use information that would be lost if every score were converted to a binary category. The trial also lists response and remission outcomes, which answer different questions by applying thresholds. Categorization may be easier to interpret as a proportion meeting a criterion, but it discards differences among participants who fall on the same side of a threshold. Neither form of analysis is inherently sufficient for every clinical question; each describes a different feature of the outcome.

What do the secondary comparisons estimate?

The response and remission outcomes are counts of participants meeting their stated criteria. For a binary outcome, the risk difference is the difference between the observed proportions in the compared arms. A risk difference near zero indicates similar observed proportions, while its interval indicates how uncertain that contrast is. The registry also lists continuous Clinical Global Impressions change. Its mean difference has the same basic interpretation as the primary mean comparison, although it concerns a different scale. These secondary results are unadjusted summary-based comparisons, and the registry does not list sponsor-reported analyses for them.

Why does multiplicity matter?

When several outcomes or analyses are examined, chance alone can produce apparently notable results. A multiplicity approach may control the overall rate of false-positive findings, but the registry does not report whether any such approach was planned or used. The secondary p values should therefore be understood as unadjusted, and they should not be treated as confirmatory findings without additional analysis-plan information. The same caution applies when interpreting a collection of outcomes rather than a single prespecified primary endpoint.

The registry lists a secondary objective of estimating an effect size for future study planning. Such an estimate is subject to sampling variability. Planning calculations that use an observed estimate are illustrations conditional on that estimate and their stated assumptions; they do not validate the original trial’s design or establish the effect that a future study will observe. The trial’s own sample-size justification and original statistical plan are not reported in the registry record.

For the primary endpoint, the listed standard deviations are 16.45 for Quetiapine XR and 8.13 for placebo. Unequal observed variability can affect the precision of a comparison and is a reason to inspect both group summaries rather than relying only on the mean difference. General statistical methods can address unequal variances in different ways, but the registry does not identify the specific test or variance assumption behind a sponsor analysis. The posted recalculation uses the summary statistics and is explicitly unadjusted.

11. Confidence Intervals and Precision

The primary mean difference is -2.5, with a reported interval from -7.814 to 2.814. This interval spans zero and includes differences in either direction. The estimate therefore has limited precision for distinguishing a negative difference from no difference or a positive difference. The interval is more informative than the point estimate alone because it conveys how much uncertainty remains around the estimated contrast.

Precision is affected by variability in outcome measurements and by the amount of information available. The standard deviations are 16.45 in the Quetiapine XR arm and 8.13 in the placebo arm, while the posted endpoint counts are 46 and 45, respectively. The observed spread is different between arms, and the estimate should be interpreted with that variation in mind. The registry does not explain the difference in counts between the endpoint groups and the recorded enrollment.

An interval that includes zero does not show that the true difference is exactly zero. Nor does it prove that any nonzero difference is meaningful. It indicates that the data, under the interval procedure, do not narrow the estimate enough to rule out zero or the other values inside the reported range. A finding of equivalence would require a prespecified equivalence margin and an analysis designed for that purpose; neither is reported in the registry record.

The registry does not report a threshold for a clinically important HAM-D-17 difference, and the interval’s confidence level is not stated in the posted outcome details. These omissions limit how precisely the statistical uncertainty can be connected to clinical importance. The appropriate reading is to consider the direction and breadth of the estimated range, while keeping the endpoint’s clinical interpretation distinct from statistical evidence.

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 figures are participants per arm, not total participants. The registry’s planning illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It uses the observed effect as its reference and considers detecting the full observed effect, 75% of the observed effect, or 50% of the observed effect. The trial’s original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the modeled number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect and the assumptions were correct. The 90% power column gives the corresponding planning target for a 90% chance. These are design probabilities under a model, not guarantees about a future trial’s result. The figures depend on the effect used for planning and the assumptions listed in the record.

The planning figures increase when the target effect is reduced from the observed estimate to a smaller fraction of it. This is the general relationship expected in such calculations: smaller effects are harder to distinguish from random variation, so more participants are needed to attain the same modeled power. The large figures for some outcomes also reflect the small observed contrast used as the planning basis. An estimate from the trial may itself be unstable, so the illustrated targets should not be treated as definitive design recommendations.

These calculations are not observed power. They are planning illustrations based on a stated effect and assumptions; they do not measure the probability that the completed trial detected an effect. The original design rationale is not reported in the registry record, and the planning illustrations should not be read as evidence that the trial was or was not adequately designed.

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

Worked calculation for this trial

1. Observed difference Δ = -2.500; pooled standard deviation σ = 13.019.
2. n = 2 × (1.96 + 0.842)² × 13.019² / -2.500² = 425.7, rounded up to 426 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 <- -2.5                      # observed difference in means
sigma <- 13.0191631015657                     # 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(671853)
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 = 426 (80% power), 570 (90% power)
 75% of observed effect: n per arm = 757 (80% power), 1,014 (90% power)
 50% of observed effect: n per arm = 1,703 (80% power), 2,280 (90% power)
power.t.test: 426.7 
Simulated power at n = 426 per arm: 0.804 (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.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes, creating multiple opportunities to examine differences. When many outcomes are tested, the chance of observing at least one apparently unusual result by chance can rise. Statistical plans sometimes address this through multiplicity control, a prespecified testing hierarchy, or a distinction between confirmatory and exploratory analyses. Whether any such plan was used is not reported in the registry record.

The secondary p values are unadjusted. They should not be interpreted as if each were the sole planned test, and they do not by themselves establish confirmatory evidence. The primary outcome remains the central comparison identified in the results. The registry’s secondary objective of generating effect-size estimates is consistent with an exploratory role for some outcomes, but the record does not state a formal testing hierarchy or identify which secondary analyses, if any, were intended to be confirmatory.

Missing-data handling is also not reported in the registry record. The endpoint counts differ from the recorded enrollment, but the record does not state why, whether data were missing, or how missing observations were handled. It does not describe an intention-to-treat population, a per-protocol population, imputation, or sensitivity analyses. Consequently, the posted group counts alone cannot establish the analysis population or the potential influence of missing outcomes.

The registry does not report baseline-adjusted models, covariates, subgroup analyses, interim analyses, stopping rules, or the original statistical analysis plan. These details matter because they affect how estimates are produced and how much confidence can be placed in selected results. Their absence does not show that a method was not used; it means the relevant method is not reported in the registry record.

Without these details, the posted results are most transparently read as group summaries and unadjusted comparisons. They support a descriptive account of the observed data, but do not allow a complete audit of outcome selection, missing-data assumptions, or multiplicity control. Further information from a protocol or analysis report would be needed to resolve those questions.

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 non-serious adverse event terms

The registry reports zero serious adverse events among 46 participants at risk in the Quetiapine XR group and zero among 45 at risk in the placebo group. No serious adverse-event terms are listed. These figures describe the posted serious-event counts for the registry record; they do not establish that serious events were impossible or that the treatments have identical safety profiles.

For other adverse events, the record lists 44 participants affected among 46 at risk in the Quetiapine XR group and 37 among 45 at risk in the placebo group. These are participant counts, not an assessment of the severity, duration, or causal relationship of each event. The registry does not provide event-level details in the listed results.

Deaths are not reported in the registry record. The absence of a death count should not be interpreted as a count of zero. Safety comparisons also depend on how events were defined, collected, and attributed; those details are not reported in the registry record. These counts describe only the posted safety data and do not provide medical advice.

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

The primary endpoint shows average HAM-D-17 score reductions in both arms during Week 0 to Week 8. The estimated between-arm difference is in the direction of a larger average reduction with Quetiapine XR, but the reported interval includes zero and extends to differences on either side. The posted data therefore do not establish a clear between-arm difference, while also not establishing that the groups are equivalent.

A non-significant unadjusted p value does not mean there is no effect, just as a numerical difference in group means does not establish an effect. Statistical interpretation depends on the estimated size, uncertainty, design, outcome definition, and analysis assumptions. Here, the interval is broad relative to the point estimate, and the registry does not report a clinically important difference threshold. The clinical importance of the estimated contrast cannot be determined from the posted summary alone.

The endpoint measures depression severity on a scale, not every aspect of a participant’s health or experience. The secondary measures address related but distinct outcomes, and their unadjusted results do not resolve the uncertainty around the primary comparison. Results for some listed secondary outcomes are not reported in the registry record.

The trial is randomized and triple-masked according to the registry, features intended to support a fair comparison and reduce bias. However, details about masking roles, allocation procedures, missing data, analysis populations, and the prespecified statistical plan are not reported in the registry record. These limits constrain how fully the posted findings can be evaluated.

Overall, the registry supports a cautious description of the observed score changes and their uncertainty. It does not justify a definitive claim that Quetiapine XR is effective or ineffective for the stated population, nor does it establish equivalence with placebo. Clinical decisions require broader evidence and individual assessment, which are beyond what this statistical summary can determine.

17. Why This Trial Matters Statistically

This trial illustrates why a point estimate should not be read in isolation. The primary comparison has a direction and magnitude, but the interval shows that the estimate remains compatible with a range of possible effects. Statistical interpretation is therefore not a binary exercise of labeling results positive or negative; it requires considering the estimated difference, its precision, the outcome’s meaning, and the analysis context together.

The record also shows the distinction between continuous and threshold-based outcomes. A mean change uses score information across the scale, while response and remission reduce outcomes to whether a criterion was met. Those approaches can be complementary, but they do not answer identical questions. Examining several outcomes without reported multiplicity control also raises the importance of separating exploratory patterns from confirmatory evidence.

Finally, the registry’s stated goal of generating effect-size estimates for future research highlights a central planning challenge. Observed effects are uncertain and may not be stable estimates of effects in a larger study. Planning illustrations can show how participant requirements change when the assumed effect changes, but they cannot replace a prespecified design rationale or justify treating the observed estimate as a known truth.

For clinical researchers, the record is a reminder to distinguish what is posted from what remains undocumented. The randomized, masked design is relevant context, while missing details about analysis populations, missing data, and multiplicity limit interpretive completeness. Transparent reporting of these elements is essential for assessing the robustness and scope of a trial’s conclusions.

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.

The registry record leaves several trial-specific questions unresolved. It does not give detailed eligibility criteria or describe the enrolled population beyond the stated bipolar disorder and comorbid generalized anxiety disorder context, with or without substance use disorder. The primary-outcome population field is blank. The record therefore does not permit a detailed assessment of how broadly the findings apply to particular patient groups.

Although the registry labels the trial randomized and triple-masked, it does not describe sequence generation, allocation concealment, or which parties were masked. It also does not explain how Quetiapine XR monotherapy and adjunctive therapy were represented in the intervention arm. Treatment procedures, adherence, concomitant care, and reasons for endpoint counts differing from recorded enrollment are not reported in the registry record.

The primary results are posted as group summaries and an unadjusted comparison. The registry does not provide the original analysis plan, the sponsor’s inferential analysis, a baseline-adjusted estimate, or an account of missing-data methods. It does not report a multiplicity strategy for the several outcomes. These omissions make it difficult to assess whether the displayed comparisons match a prespecified plan or how sensitive they might be to analytic choices.

Some listed secondary outcomes lack posted results, including quality-of-life and anxiety measures. The record also does not state a clinically important difference threshold for the primary scale or the confidence level associated with its interval. Safety information is limited to group counts, without event-level descriptions, attribution details, or a reported death count. These limitations restrict both clinical interpretation and independent evaluation of the findings.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Quetiapine Extended Release (XR) in Bipolar Patients With Comorbid Generalized Anxiety Disorder (GAD) — NCT00671853.
• Registry record last updated 2016-12-29; status last verified 2016-11.
• Results first posted 2013-10-11.
• 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

The registry describes a completed randomized, triple-masked, parallel Phase 3 trial of Quetiapine XR versus placebo in bipolar patients with comorbid generalized anxiety disorder. Recorded enrollment is 120. The primary endpoint is change in HAM-D-17 score from Week 0 to Week 8.

The posted mean changes were -9.91 with Quetiapine XR and -7.41 with placebo. The unadjusted mean difference was -2.5, with an interval from -7.814 to 2.814 and an unadjusted p value of 0.357. The interval includes zero, so the primary comparison remains uncertain.

Reported secondary outcomes and adverse-event counts provide additional descriptive context, but the registry does not report a multiplicity plan, missing-data methods, analysis populations, or the original statistical plan. The posted results should be interpreted as registry summaries rather than a complete account of the trial analysis.