This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for GABA Mechanisms Underlying the Vulnerability to Alcohol Dependence (NCT00611767), a randomized na study. The primary outcome is Visual Analog Scales of Similarity to Alcohol - Baseline.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00611767 |
| Phase | NA |
| Condition | Alcoholism |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 73 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Yale University |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns people with and without a family history of alcohol dependence. The registry summary describes the family-history-positive group as having no current Axis I disorder other than nicotine dependence, and says the comparison group was age-matched. The eligibility details and the precise definition of a positive or negative family history are not reported in the registry record.
Intervention
The interventions were thiopental, a GABAA receptor agonist barbiturate, and placebo. The arm descriptions say participants in each family-history group would receive both interventions, consistent with the crossover design. Doses, administration details, and the order in which participants received the interventions are not reported in the registry record.
Comparator
The relevant treatment contrast is thiopental versus placebo within a crossover study, while family-history status defines the groups of interest. The study summary asks whether the reward valence of thiopental differs by family-history status. The record does not give a numerical treatment comparison or a numerical comparison between the family-history groups.
Primary question
The central hypothesis concerns whether people with a family history of alcohol dependence experience the effects of thiopental as more or less alcohol-like than people without that family history. The record also describes a hypothesis that variation in genes involved in brain GABA function may influence risk for alcoholism by altering a component of ethanol’s discriminative stimulus effects. No genetic result or result for the family-history hypothesis is reported in the registry record.
These are related but not identical questions. A self-report of similarity to alcohol captures a participant’s subjective impression; it is not, by itself, a measure of alcohol consumption or a diagnosis of alcohol dependence. The registry identifies Visual Analog Scales of Similarity to Alcohol at baseline as the primary outcome, while the study summary describes broader questions about drug effects and vulnerability. Because the posted record does not report outcome estimates, it cannot establish whether the observed responses differed by family-history group or intervention.
3. Trial Design
The registry describes a randomized, double-masked crossover study with thiopental and placebo. In a crossover design, participants receive more than one intervention, so comparisons may use information from the same participant under different intervention conditions. The arm descriptions state that both the family-history-negative and family-history-positive groups receive two interventions. Family-history status is a grouping characteristic, not an intervention assignment.
The registry lists enrollment as 73, identifies Yale University as the sponsor, and gives the study status as completed. The recorded start is 2005-11 and primary completion is 2012-04. Phase is listed as NA. These registry entries describe the study record; they do not establish how many participants contributed usable observations to a particular outcome analysis.
The study summary frames the research around GABA-related mechanisms, the subjective effects of thiopental, family history of alcohol dependence, and possible genetic influences on ethanol’s discriminative stimulus effects. Thiopental and placebo are the listed drug interventions. The summary also describes the family-history-negative group as age-matched to the positive group, but the matching procedure is not reported in the registry record.
Important operational details are not reported in the registry record, including intervention sequence, washout interval, dose, administration schedule, and the method used to preserve masking. The record does not describe how randomization was generated or concealed, or whether participants, investigators, and outcome assessors were all masked. These omissions limit assessment of the crossover implementation and the risk of sequence, period, or carryover effects.
Although crossover studies can support within-participant comparisons, their interpretation depends on the timing and conduct of each treatment period. The registry record does not provide enough detail to assess those features. The completed status also does not itself indicate that results were posted or that the study’s hypotheses were confirmed.
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.
Overall Study
| Stage | Family History Negative for Alcoholism | Family History Positive for Alcoholism |
|---|---|---|
| STARTED | 49 | 24 |
| Thiopental Test Day | 3 | 1 |
| Placebo Test Day | 6 | 1 |
| COMPLETED | 40 | 22 |
| NOT COMPLETED | 9 | 2 |
Reasons for not completing this period:
| Reason | Family History Negative for Alcoholism | Family History Positive for Alcoholism |
|---|---|---|
| Withdrawal by Subject | 4 | 1 |
| Thiopental not available | 3 | 0 |
| didn't like the medication | 1 | 1 |
| Physician Decision | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: All available data was utilized in the analysis using mixed models.
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.
| Characteristic | Unit | Family History Negative for Alcoholism | Family History Positive for Alcoholism | Total |
|---|---|---|---|---|
| Participants analysed | 49 | 24 | 73 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 49 | 24 | 73 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 24.02 (SD 2.5) | 24.63 (SD 3.06) | 24.22 (SD 2.69) |
| Sex: Female, Male: Female | Participants | 25 | 10 | 35 |
| Sex: Female, Male: Male | Participants | 24 | 14 | 38 |
| Region of Enrollment: United States | participants | 49 | 24 | 73 |
6. Primary Endpoint
The registry lists the primary outcome as Visual Analog Scales of Similarity to Alcohol - Baseline, measured over Baseline.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary outcome is titled Visual Analog Scales of Similarity to Alcohol - Baseline. It measures how similar the perceived effects of a drug are to alcohol, using a Likert scale from 0, meaning not at all similar to alcohol, to 7, meaning extremely similar to alcohol. The registered outcome is continuous, with the mean as its parameter and standard deviation as its dispersion measure. Its timeframe is baseline.
This kind of subjective rating is relevant to the study’s stated interest in the discriminative stimulus effects of ethanol and whether thiopental produces effects perceived as alcohol-like. It records a participant’s reported similarity judgment rather than a biological measure or a direct measure of alcohol use. A mean can describe the central tendency of ratings, while a standard deviation describes how spread out those ratings are. Neither summary, alone, explains why individual responses vary.
The baseline timing is important. The registry title identifies this measure as baseline, so it should not be described as a post-intervention result. The record does not provide a numerical mean, standard deviation, treatment contrast, or group contrast for this outcome. It also does not report how baseline ratings were combined with later assessments, if any. The listed scale therefore clarifies what was intended to be measured, but the posted record does not show the resulting level or pattern of responses.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically motivated hypothesis, a crossover design, and a subjective primary measure, but it does not report numerical results for the primary outcome. Consequently, there is no posted estimate in this record from which to describe the direction, size, or precision of a thiopental-versus-placebo contrast, or a difference by family-history status. A completed study status is not a substitute for an outcome estimate.
The primary measure is specifically labeled baseline. That label matters when interpreting any claim about an intervention: a baseline rating describes a starting assessment, not necessarily a response after thiopental or placebo. The registry record does not state how the baseline measure relates analytically to subsequent ratings. It would therefore be unwarranted to treat the registered outcome title as evidence of an intervention effect.
The record says that all available data were used in analysis with mixed models. This indicates an analysis approach intended to use available observations, but the model specification and its numerical output are not reported. There is no posted estimate, confidence interval, or p-value for the primary outcome in the record. Without an estimate and its uncertainty, readers cannot judge whether the data are compatible with a range of effect sizes or how precisely a treatment or group contrast was measured.
The study summary describes hypotheses about family history and GABA-related effects, and mentions possible genetic influences. Those statements define the motivation for the research; they are not findings. No genetic results, family-history comparison, or outcome-specific estimates are reported in the registry record. Nor does the record provide results for the numerous secondary outcome measures it lists.
The safety entries list zero serious adverse events and zero other adverse events in each family-history group, with 49 at risk in the family-history-negative group and 24 at risk in the family-history-positive group. These are registry counts for the stated groups. The record does not supply additional detail about event collection, observation windows, or completeness of reporting, and deaths are not numerically reported. These entries should be read as the registry’s recorded counts, not as proof that no unrecorded events occurred.
Overall, the record supports a description of the research question and design, but not a conclusion about whether the measured responses differed. Statistical interpretation requires the observed estimates, their uncertainty, and the analysis details. Those outcome results are not reported in the registry record.
9. Statistical Methods Explained
The registry identifies the primary measure as continuous and describes its parameter as a mean, with standard deviation as the dispersion measure. A mean summarizes the average rating in the observations included in an analysis. A standard deviation describes how much individual ratings vary around that average. These summaries answer different questions: the mean concerns the center of the distribution, while the standard deviation concerns its spread. Neither is a measure of precision for a comparison by itself.
What does a crossover design contribute?
In general, a crossover design allows an intervention comparison to draw on observations from the same participant under different treatment conditions. Because a participant’s responses can be related across periods, an appropriate analysis generally needs to account for that within-participant dependence. This can improve the efficiency of a comparison when the design is conducted and analyzed appropriately. It does not remove the need to consider period effects, sequence effects, or carryover from an earlier intervention.
The registry labels this study randomized, double-masked, and crossover, and lists thiopental and placebo. It does not report the intervention sequence, period structure, washout, or the statistical handling of period or carryover effects. Those details are needed to judge how the crossover data were structured and whether the analysis reflected that structure. The statement that mixed models were used does not, on its own, specify which effects were included or how the covariance among repeated observations was handled.
What does a mixed model generally do?
In general, a mixed model can represent both systematic features of a study and dependence among observations from the same participant. Fixed effects can represent contrasts or factors of scientific interest, while random effects can represent participant-level variation. The precise terms, link or outcome distribution, covariance structure, and estimation approach depend on the research question and data. The registry record says that mixed models were used with all available data, but does not report these specifications. It is therefore not possible to reconstruct the fitted model or determine which contrasts it estimated.
Using all available observations in a model does not mean that every participant contributed data to every outcome or assessment. In general, model-based use of incomplete observations relies on assumptions about the missing-data process and the model. The registry record does not report the amount or pattern of missing data, the reasons observations may have been absent, or sensitivity analyses addressing missingness. The phrase all available data describes the stated analysis population approach; it does not establish that missingness had no effect.
How should uncertainty be assessed?
In general, an estimate describes the size and direction of an observed contrast, while a confidence interval describes a range of values compatible with the data under the method’s assumptions. A narrow interval indicates greater precision than a wide interval, though neither guarantees that the model or design assumptions are correct. A p-value, when reported, addresses compatibility with a specified null hypothesis under an analysis framework; it does not measure the probability that the null hypothesis is true or the clinical importance of an effect.
No primary-outcome estimate, confidence interval, or p-value is reported in the registry record. The record lists zero analysis entries, so there is no registered analysis result available to interpret for the endpoint. The registry’s description of an analysis method should not be mistaken for evidence of a treatment difference.
How should a planning illustration be read?
In general, sample-size calculations are planning tools: they describe how much information a hypothetical study might need under stated assumptions. They are not observed power, and they cannot replace the effect estimate and uncertainty from the completed study. The planning assumptions described for the illustration use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. The stated basis is the observed effect, not the trial’s own design justification. The record does not report a sample-size justification for this trial.
The planning assumptions use an equal-allocation two-arm framing, whereas the registered study is a crossover with thiopental and placebo and groups defined by family history. A planning illustration under simplified assumptions should therefore be read as a hypothetical exercise, not as a description of the actual randomization or analysis. No planning result is reported in the registry record, and no calculation should be taken as a study finding.
Finally, the primary outcome’s baseline label and the registry’s note that the primary outcome has several categories or time points, and was not reduced to one comparison, constrain interpretation. A single mean or contrast cannot be inferred from that description. The record does not specify a single primary contrast, how multiple observations entered the model, or how estimates were selected for reporting. Such choices matter because different legitimate contrasts can answer different questions.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 78 outcome measures and names several secondary outcomes, including ratings of the number of drinks participants felt they had consumed at multiple post-baseline time points and a baseline stimulant subscale of the Biphasic Alcohol Effects Scale. The registry record lists zero analysis entries. It does not report which outcomes were analyzed, which comparisons were prespecified, or which results were selected for reporting.
In general, testing many outcomes or time points creates multiple opportunities to observe apparently notable findings by chance. Multiplicity procedures can help control the error rate across a defined family of comparisons, but the appropriate approach depends on which outcomes and contrasts are considered together. The registry record does not report a multiplicity strategy, hierarchy of outcomes, or adjustment procedure. No conclusion can be drawn about whether any unreported analyses were adjusted.
The primary outcome is described as having several categories or time points and is not reduced to one comparison in the record. That means a single numerical summary should not be assumed to represent every relevant response pattern. The record does not specify the intended primary contrast across treatment, family-history group, or time.
The population description for the primary analysis says all available data were utilized using mixed models. This is not a complete account of missing-data handling. The amount and pattern of missingness, reasons for missing observations, imputation procedures, and sensitivity analyses are not reported in the registry record. The exact analysis population for each outcome is also not reported. These omissions limit assessment of how representative the analyzed observations were and how robust inferences might be to missing data.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Family History Negative for Alcoholism | 0 | 49 | 0.0% |
| Family History Positive for Alcoholism | 0 | 24 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Family History Negative for Alcoholism | 0 of 49 |
| Family History Positive for Alcoholism | 0 of 24 |
The registry reports adverse-event counts separately for the family-history-negative and family-history-positive groups. For serious adverse events, the listed number affected is 0 in each group; for other adverse events, the listed number affected is also 0 in each group. The corresponding numbers at risk are 49 for the family-history-negative group and 24 for the family-history-positive group.
These are safety entries grouped by family-history status, not a reported comparison of thiopental with placebo. The record does not give event descriptions because no serious terms are listed, and it does not report how adverse events were defined, collected, or attributed to an intervention. The observation period and completeness of safety follow-up are not reported in the registry record.
Deaths are not given as numerical counts in the record. A blank or null death entry should not be read as a confirmed count of zero. More generally, the posted zero event counts describe what the registry records for these categories; without details on monitoring and reporting, they do not establish that no events occurred outside the recorded data.
12. What the Result Does, and Does Not, Mean
The study addresses a question about whether subjective responses to thiopental are related to family history of alcohol dependence, with placebo as the other intervention in a randomized, double-masked crossover design. Its primary measure concerns perceived similarity to alcohol. This combination of a pharmacologic intervention, family-history grouping, and self-reported response makes the question relevant to the study’s stated interest in GABA mechanisms and alcohol-like drug effects.
The registry record does not report numerical results for the primary outcome. It therefore does not establish the direction or size of any treatment contrast, whether family-history groups differed, or how precise any estimated difference was. No conclusion about support for the study hypotheses can be drawn from the stated aims and design alone. The record also does not report genetic findings, despite describing a genetic hypothesis in its summary.
A rating of similarity to alcohol is a subjective outcome. It can describe how participants characterize an experience, but it does not directly measure alcohol consumption, alcohol dependence, or long-term risk. Likewise, a short-term response to thiopental would not by itself establish how a person will respond to alcohol in everyday settings. The record does not provide results that would allow even a narrow claim about the measured rating.
The baseline timing attached to the primary outcome further limits interpretation as an intervention effect. A baseline measurement is not automatically a response to treatment. The registry does not report a model contrast or explain how that measure was related to later assessments. Readers should distinguish the study’s hypothesis from the results actually reported.
The safety entries report zero serious and zero other adverse events in the two family-history groups, but the registry provides limited context for interpreting those counts and does not numerically report deaths. Those entries should not be expanded into broad claims about safety. The study record is informative about the research question, design labels, planned outcome, and recorded safety counts, but it does not supply the estimates needed to assess efficacy or the precision of an effect.
13. Why This Trial Matters Statistically
This study illustrates why the design and the exact endpoint definition matter when reading a clinical trial record. A randomized, double-masked crossover design has a different comparison structure from a parallel-group study: the same participant is intended to receive thiopental and placebo, while family-history status distinguishes groups. Keeping those two dimensions separate is essential. A family-history comparison is not itself the randomized treatment contrast.
The endpoint also requires careful reading. Visual Analog Scales of Similarity to Alcohol assesses a subjective judgment, and the registry labels the measure baseline. It would be easy to conflate that endpoint with a later treatment response or with alcohol use, but those are not interchangeable outcomes. Clear timing and measurement definitions prevent claims from exceeding what an endpoint can support.
The record also shows the limits of design descriptions without results. Mixed models are identified, but the model specification and outcome estimates are absent. A method label cannot establish whether a contrast was large, small, precise, or compatible with no difference. Similarly, a completed status does not convey the findings. Readers need estimates and uncertainty, along with enough analysis detail to connect them to the design.
Finally, the registry lists many outcome measures but no analysis entries. This highlights why prespecification, multiplicity planning, and transparent reporting are important: a reader needs to know which comparisons were primary and how multiple outcomes were handled. The record leaves those questions unanswered. Statistically, the study is a useful example of how a biologically motivated question, subjective endpoint, crossover structure, missing model detail, and absent result estimates all shape the limits of interpretation.
14. 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 details needed for a full design assessment are not reported in the registry record. The intervention doses, administration schedule, treatment sequence, period structure, and washout interval are not given. Without these, it is not possible to assess how the crossover was implemented or whether order and carryover effects were considered.
The record does not describe the randomization method, allocation concealment, or the practical procedures used to maintain double masking. It does not report the exact family-history definitions, recruitment process, or matching procedure for the age-matched comparison described in the summary. The primary analysis is said to use all available data in mixed models, but the model terms, covariance structure, and handling of repeated observations are not specified.
Most importantly, the registry does not report numerical results for the primary outcome, and it lists zero analysis entries. No outcome estimates or measures of uncertainty are available for assessing the stated hypothesis. Although the record lists 78 outcome measures, it does not report a multiplicity strategy, the analysis population for each measure, or which secondary outcomes were analyzed.
Missing-data amounts and patterns, reasons for missingness, and sensitivity analyses are not reported. Safety monitoring details and the observation window are also absent, while deaths are not numerically reported. These gaps restrict interpretation of both outcomes and safety counts. The listed enrollment and adverse-event denominators should not be assumed to equal the number contributing to every analysis.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: GABA Mechanisms Underlying the Vulnerability to Alcohol Dependence — NCT00611767.
- Registry record last updated 2017-03-17; status last verified 2016-11.
- Results first posted 2017-03-17.
- 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.
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18. Record Summary
The registry record describes NCT00611767, a completed randomized, double-masked crossover study sponsored by Yale University. It lists thiopental and placebo as interventions and defines groups by positive or negative family history of alcoholism. Enrollment is listed as 73; the recorded study start is 2005-11 and primary completion is 2012-04. Phase is listed as NA.
The primary outcome is a baseline rating of similarity to alcohol on a scale from 0 to 7. The record says all available data were analyzed using mixed models, but does not report the model specification or numerical outcome results. It lists 78 outcome measures and zero analysis entries. Safety counts list zero serious and zero other adverse events in each family-history group; deaths are not numerically reported.
The record explains the study’s hypotheses and design, but does not provide results with which to assess the primary question or its precision.