Gamma-Amino Butyric Acid (GABA)-A Alpha2/3 Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gamma-Amino Butyric Acid (GABA)-A Alpha2/3 Study (NCT00129441), a randomized phase 2 study. The primary outcome is N-back Task - Reaction Time.

2. Clinical Question

The endpoint focuses on a component of working memory performance. In the N-back task, a participant responds when the current letter matches the letter shown a specified number of steps earlier. The primary measure used the 2-back condition, which places a working-memory demand on the respondent. The registry description identifies this condition as the task’s best index of performance and of dorsolateral prefrontal cortex disturbances in subjects with schizophrenia.

The result is a comparison of group means among participants who completed the trial and had an available week-4 N-back result. It is not a comparison of every enrolled participant: one participant refused the week-4 N-back task, and the reported analysis groups contained 9 and 5 participants. How the other enrolled participants were handled or why they were not included in this endpoint analysis is not reported in the registry record.

The clinical question is therefore specific to a short-term cognitive task measure in this study population. It is not, by itself, a broad assessment of cognition, psychiatric symptoms, daily functioning, or longer-term outcomes. The registry also lists psychiatric-rating and neuropsychological measures among secondary outcomes, but the primary question concerns N-back reaction time.

3. Trial Design

This was a Phase 2 randomized, triple-masked, parallel-group study sponsored by the University of Pittsburgh. The registry marks the trial as completed, with enrollment of 16. The listed condition is schizophrenia. The brief study description specifies a group of stable male subjects with schizophrenia and describes the aim as assessing whether short-term administration of an investigational drug could provide evidence of cognitive improvement.

Participants were assigned to L-830982 or placebo. The registry identifies the interventions as drug interventions and lists L-830982 and placebo as the outcome arms. It does not report the allocation ratio, the randomization procedure, or further details about who was masked under the triple-masking designation. Those design details are not reported in the registry record.

The primary endpoint was assessed at Week 4. The trial is described as parallel rather than crossover, so the two arms represent separate groups rather than participants switching between treatments in the reported design. The endpoint analysis included participants who completed the 4-week trial: 9 participants in the L-830982 arm and 5 in the placebo arm. One participant refused the week-4 N-back assessment. The registry does not give a full account of participant flow or reasons for all exclusions from this endpoint analysis.

The study started in 2005-08 and its primary completion date was 2008-01. These dates describe the recorded trial timeline; they do not establish the duration of treatment for each participant beyond the brief description of short-term administration and the Week 4 endpoint. Details such as the planned treatment schedule, dose, eligibility criteria beyond the stated population, and sample-size justification are not reported in the registry record.

Several secondary outcomes are listed, including the Brief Psychiatric Rating Scale Total Score, the RBANS Total Score, and the RBANS Delayed Memory Subindex. The record lists 8 outcome measures and 8 analyses. The specific analysis plans and any hierarchy among outcomes are 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: To ensure eligibility before randomization, the following were administered: a urine drug screen; diagnostic, medical history and adverse events ratings; Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); electrocardiogram; blood tests (for kidney and liver function); and a complete eye exam, including a slit-lamp exam.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Analyses included only those participants who completed the 4-week trial. One participant refused N-back at week-4, so 9 L-830982 and 5 placebo were analyzed.

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 N-back Task - Reaction Time, measured over Week 4.

The primary endpoint is mean reaction time, in milliseconds, on the 2-back condition of the N-back task at Week 4. The task presents a sequence of letters and asks the participant to respond when a current letter matches one shown a certain number of steps earlier. The 2-back condition requires the participant to keep track of recent stimuli and compare the current stimulus with one encountered earlier in the sequence.

Reaction time measures the time taken to respond. As a general interpretation of this type of measure, a shorter response latency indicates a quicker response on the task; it does not on its own describe accuracy or the full quality of working-memory performance. The registry identifies the 2-back condition as the best index in this task of performance and of dorsolateral prefrontal cortex disturbances in subjects with schizophrenia. That rationale explains why this condition was selected as the primary measure, but it does not make the task a comprehensive measure of cognition.

The reported outcome is continuous and is summarized with a mean and standard deviation for each arm. The L-830982 group had a mean of 786.0 msec and a standard deviation of 231.0; the placebo group had a mean of 684.0 msec and a standard deviation of 101.0. The analysis used week-4 completers with an available N-back result. Accuracy results, individual participant data, and a confidence interval for the arm contrast are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the mean describe?

A mean is the arithmetic average of the observed measurements in a group. Here, it summarizes reaction times in milliseconds among participants included in the week-4 endpoint analysis. The reported means are 786.0 msec for L-830982 and 684.0 msec for placebo. A group mean gives a compact description of the data, but it does not show the full distribution, the range of individual responses, or whether the result is driven by a small number of observations.

The standard deviation describes how dispersed observations are around their group mean. The reported standard deviations are 231.0 for L-830982 and 101.0 for placebo. A larger standard deviation indicates greater spread in the observed measurements, not a larger treatment effect. Standard deviations are also estimates from the analyzed participants; they do not establish how much variability would be seen in a broader population.

What does the ANOVA test?

ANOVA, or analysis of variance, is a general method for assessing differences among group means. In a two-arm comparison such as the one reported, the analysis addresses whether the observed data are consistent with a null model that has no difference in mean outcome between groups. The registry reports an ANOVA p-value of 0.16. The specific ANOVA model, its included terms, and any adjustments are not reported in the registry record, so the label alone does not establish exactly how the test was implemented.

As a general statistical concept, a p-value is calculated under a null model and its assumptions. It represents the probability of observing data at least as incompatible with that model as the observed data, if the null model were true. It is not the probability that the null hypothesis is true, and it is not the probability that a result is due to chance. It also does not measure the magnitude of a difference or the practical importance of an outcome.

Why is uncertainty important?

A confidence interval gives a range of values compatible with the data under a specified procedure and its assumptions. It conveys uncertainty about an estimate more directly than a p-value alone because it displays both the estimated contrast and its precision. The registry associates a 95% confidence level with the reported analysis, but the confidence-interval limits and the estimated contrast are not reported in the registry record. Without those values, the precision and range of plausible contrasts cannot be read from the posted inferential result.

As a general matter, a confidence interval is not a guarantee that the true value lies inside that particular interval. Its coverage interpretation concerns the long-run performance of the procedure under its assumptions. The assumptions and construction method for a confidence interval are not detailed in the registry record.

What can a small analysis group mean?

The endpoint analysis contains 9 L-830982 participants and 5 placebo participants. With small groups, estimates of means and standard deviations can be sensitive to individual observations. Statistical tests may also have limited ability to distinguish a real difference from sampling variation. This is a general limitation of small samples, not a claim about the reason for this trial’s observed p-value. The record does not report the sample-size justification or a prespecified power calculation, so the study’s planning rationale cannot be assessed from the registry entry.

For continuous outcomes, common model assumptions may concern the distribution of residuals, independence of observations, and how variability behaves across groups. Whether these assumptions were checked, whether transformations were considered, or whether an alternative model was used is not reported in the registry record. The reported means and standard deviations alone do not establish that an analysis assumption was met or violated.

How should the analysis population be understood?

The registry says that the primary analysis included only participants who completed the 4-week trial. It also notes that one participant refused the week-4 N-back task. This describes a completer-based endpoint analysis, not necessarily an analysis of every randomized participant. The record does not report an intention-to-treat analysis, an imputation approach, or a sensitivity analysis for missing endpoint measurements. As a general concept, different approaches to missing outcomes can rely on different assumptions; without a reported approach, the effect of missing data cannot be evaluated.

What do planning illustrations represent?

Sample-size planning illustrations are hypothetical calculations based on stated assumptions; they are not observed power. In this record, the stated illustration assumptions include a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of the observed effect. The actual design rationale and sample-size justification are not reported in the registry record. Any planning illustration should therefore be distinguished from the observed trial results and should not be used as evidence that the study had a particular probability of detecting an effect.

In general, planning calculations depend on the chosen target effect, variability assumptions, allocation, and testing procedure. Because the record does not report the original design justification, it is not possible to tell whether the study’s enrollment was chosen using those assumptions or another rationale.

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("L-830982", "Placebo")
n   <- c(9, 5)
m   <- c(786, 684)
sp  <- c(231, 101)
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  L-830982  9  786.000  231.000  608.438  963.562
CARM  Placebo  5  684.000  101.000  558.592  809.408

11. Analyses Reported by the Sponsor

The registry reports the primary comparison as an ANOVA with p = 0.16. It does not report an estimated between-arm contrast, a confidence interval for that contrast, or enough model detail to reconstruct the sponsor’s analysis from the group summaries alone. The mean and standard deviation in each arm are descriptive summaries, while the p-value is the reported inferential result.

A simple re-calculation from posted summary statistics is not available for this continuous two-arm comparison in the registry record. The posted information does not include the needed inferential quantities or a recalculated contrast. Consequently, there is no independently recalculated estimate to compare numerically with the reported ANOVA result.

The registry does not mark a discrepancy between a sponsor-reported result and a recalculated result. The sponsor’s reported analysis therefore remains the available inferential analysis. Its p-value should still be interpreted within the limits of what is recorded: the analysis population is restricted to trial completers with an available N-back result, the groups are small, and the model details and uncertainty interval are not reported. The posted data allow the arm means and standard deviations to be described, but they do not permit a full independent assessment of the sponsor’s model or its precision.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes in addition to the primary N-back reaction-time endpoint. These include the Brief Psychiatric Rating Scale Total Score, the Repeatable Battery for the Assessment of Neuropsychological Status Total Score, and its Delayed Memory Subindex. The record lists 8 outcome measures and 8 analyses. This indicates that the recorded results cover multiple measures, but the registry does not report a formal outcome hierarchy or explain how the primary and secondary tests were coordinated.

When multiple outcomes or comparisons are analyzed, the chance of obtaining at least one apparently notable result can increase if each test is interpreted separately. As a general statistical concept, multiplicity procedures can control error rates across a defined family of tests. Whether any such correction was planned or applied in this trial is not reported in the registry record. The p-value of 0.16 should therefore be read as the reported result for the primary comparison, without assuming either that a multiplicity adjustment was made or that it was unnecessary.

The primary analysis population is described as participants who completed the 4-week trial. The registry specifically notes one refusal of the week-4 N-back task and reports 9 L-830982 participants and 5 placebo participants in the analysis. It does not report a complete participant-flow account, reasons for all participants not represented in the endpoint analysis, or whether those reasons differed by arm. The disposition of missing primary outcomes beyond the noted refusal is not reported in the registry record.

The record does not report imputation, a missing-data model, an intention-to-treat analysis, or sensitivity analyses. These methods address different assumptions about unavailable outcomes; none should be inferred from the fact that a completer analysis was reported. The protocol’s planned analysis population, interim analyses, and statistical analysis plan are not reported in the registry record. Without those details, it is not possible to determine whether the posted analysis follows a prespecified plan or how robust it is to alternative handling of missing values and multiple outcomes.

13. 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 no serious adverse events among the participants at risk in either arm: 0 among 10 in the L-830982 group and 0 among 6 in the placebo group. These are observed counts in the groups recorded for safety, not proof that serious events could not occur. The safety group sizes are not the same as the primary endpoint analysis group sizes, so the safety counts should be read using their own denominators.

For other adverse events, the registry reports 4 among 10 participants at risk in the L-830982 group and 0 among 6 in the placebo group. These counts are separate from the serious-event counts. The record does not provide further detail in the posted summary about the specific non-serious events, their severity, timing, or relationship to study treatment.

Specific serious adverse-event terms and death counts are not reported in the registry record. A missing death count should not be interpreted as a reported zero. The available figures are descriptive safety counts and do not, on their own, establish a causal relationship or provide a precise comparison between arms.

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

The posted primary result describes week-4 reaction time on a working-memory task among participants included in the endpoint analysis. It reports group means, standard deviations, and an ANOVA p-value. Together, these statistics describe the observed data and the sponsor-reported test; they do not amount to a complete estimate of the treatment contrast with uncertainty.

The result does not establish that the groups were identical. A p-value of 0.16 does not demonstrate absence of an effect, just as it does not establish an effect. Because the between-arm estimate and confidence limits are not reported in the registry record, the range of contrasts compatible with the data is not available. The group summaries alone cannot answer how precise the comparison is.

The measure is also narrower than the phrase cognitive functioning. It captures reaction time in one condition of one task at one follow-up point. The registry identifies the 2-back task as relevant to working memory and as an index of performance and dorsolateral prefrontal cortex disturbances in subjects with schizophrenia, but the primary endpoint does not cover every cognitive domain, psychiatric symptom, functional outcome, or longer-term result.

The analysis was based on trial completers with an available week-4 N-back result, rather than all 16 enrolled participants. The registry mentions one participant who refused the task, but does not give a full account of endpoint availability. As a result, the primary analysis should not automatically be generalized to every enrolled or randomized participant.

The study’s listed secondary measures and multiple outcome analyses also matter when interpreting an individual result. The registry does not report whether a multiplicity strategy was used. Nor does it report enough protocol or analysis-plan detail to establish the intended interpretation of all tests. These limitations leave the result informative as a record of the observed endpoint summaries and reported test, but insufficient for broader claims about efficacy, safety, or clinical benefit.

15. Why This Trial Matters Statistically

This trial is statistically instructive because it combines a clearly specified continuous cognitive endpoint with a small completer analysis. The primary measure—2-back reaction time at Week 4—has an intuitive unit, milliseconds, and is summarized by group means and standard deviations. Readers can see both the average observed performance and the extent of within-group variation, while also recognizing that these summaries are based on relatively few endpoint observations.

The record illustrates why an inferential test should not be read in isolation. The ANOVA p-value of 0.16 does not describe the magnitude of the contrast, and no contrast estimate or confidence limits are reported. A p-value without an effect estimate and its precision leaves important questions unanswered. This is especially relevant when group sizes are small and unequal, because the amount of information available for estimating the means and their difference is limited.

The trial also makes the analysis population visible: the endpoint result applies to participants who completed the trial and had a week-4 N-back result. One refusal is specifically noted. That detail illustrates how an apparently straightforward endpoint can depend on who contributes outcome data, while the registry’s limited participant-flow information leaves the broader missing-data picture unclear.

Finally, the record lists multiple outcome measures and analyses but does not describe a multiplicity strategy or full statistical analysis plan. This distinguishes what can be learned from registry results—observed summaries and a reported test—from what requires protocol-level documentation. Together, these features make the trial a useful example of interpreting a clinical result with attention to estimand, analysis population, uncertainty, and reporting completeness, rather than relying on a single p-value.

16. 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 analysis represents 9 participants assigned to L-830982 and 5 assigned to placebo, although the trial enrollment was 16. The registry states that only participants who completed the 4-week trial were included and notes one refusal of the week-4 N-back task. It does not report a full disposition of the enrolled participants or reasons for all exclusions from the endpoint analysis. This restricts interpretation to the recorded completer population and leaves the potential influence of missing outcomes uncertain.

The reported results do not include an estimated mean contrast or confidence-interval limits. Although a 95% confidence level is associated with the reported analysis, the interval itself is not reported in the registry record. The p-value alone cannot convey the range of contrasts compatible with the data. Details of the ANOVA model, assumption checks, covariates, and any sensitivity analyses are also not reported.

The endpoint is a task-specific measure at Week 4. The registry describes the 2-back condition as the best index of performance and dorsolateral prefrontal cortex disturbances within the task, but the result should not be treated as a complete assessment of cognition or functioning. Accuracy and individual response data are not reported alongside the primary result.

Several secondary outcomes and 8 analyses are listed, but the approach to multiplicity is not reported. The protocol, sample-size justification, interim analyses, and statistical analysis plan are not reported in the registry record. These omissions prevent assessment of whether the completed analyses followed a prespecified hierarchy or how the enrollment target was chosen.

The safety summary reports event counts but does not provide specific serious-event terms or a death count. The available counts do not describe severity and timing for other events or establish causality. These limitations apply to interpretation of the registry results and do not establish that unreported information was absent from other study documentation.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Gamma-Amino Butyric Acid (GABA)-A Alpha2/3 Study — NCT00129441.
• Registry record last updated 2011-10-17; status last verified 2011-10.
• Results first posted 2011-10-17.
• 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.

20. Record Summary

The registry record describes a completed, randomized, triple-masked, parallel Phase 2 study sponsored by the University of Pittsburgh, with enrollment of 16 and schizophrenia listed as the condition. The study compared L-830982 with placebo in stable male subjects with schizophrenia. The primary endpoint was mean reaction time in milliseconds on the 2-back N-back task at Week 4.

The endpoint analysis included 9 L-830982 participants and 5 placebo participants who completed the 4-week trial. Their reported means were 786.0 msec and 684.0 msec, with standard deviations of 231.0 and 101.0. The registry reports an ANOVA p-value of 0.16, but does not report the estimated contrast or confidence-interval limits.

The record lists multiple secondary outcomes and analyses. Full participant flow, missing-data methods, multiplicity handling, the sample-size justification, and details of the statistical analysis plan are not reported in the registry record.