Pharmacogenetic Treatment With Anti-Glutaminergic Agents for Comorbid PTSD & AUD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacogenetic Treatment With Anti-Glutaminergic Agents for Comorbid PTSD & AUD (NCT02884908), a randomized phase 3 study. The primary outcome is Heavy Drinking Days as Measured by the Time Line Follow Back (TLFB).

2. Clinical Question

The clinical question combines a treatment comparison with a pharmacogenetic focus: the study concerns pregabalin versus placebo in participants selected by genotype, with BBCET included in both conditions. The registry lists four treatment-by-genotype groups, but the precise planned contrasts between those groups are not reported in the registry record. In particular, the record does not give a numerical estimate for the treatment effect within either genotype category or an estimate of whether treatment effects differed by genotype. The stated secondary objective was to assess safety and tolerability in people with co-occurring AUD and PTSD who had selected genotypes. The record describes a completed trial with enrollment of 57, while the primary-outcome analysis population was 44 participants who took at least 1 dose. These are distinct counts: enrollment describes the trial, while the latter count defines the stated analysis population for the primary outcome.

3. Trial Design

The registry classifies this as a phase 3, randomized, quadruple-masked, factorial trial. It lists enrollment of 57 and a completed status. The recorded start date is 2017-07-07 and the primary completion date is 2022-01-19. The sponsor is the University of Maryland, Baltimore.

The intervention comparison was pregabalin plus BBCET versus placebo plus BBCET. The arm descriptions subdivide each condition by genotype: NI/I/II type and NI/NI type. This means the registry presents a factorial structure involving medication assignment and genotype groups. The precise allocation scheme within the genotype groups, the intended statistical contrasts, and whether genotype was used as a randomization factor are not reported in the registry record. “Factorial” describes the recorded design classification; it does not, by itself, establish which interaction tests or subgroup comparisons were planned.

Randomization is intended to make treatment groups comparable on average, while masking is intended to limit the influence of treatment knowledge on participant experience, clinical care, and outcome assessment. Those are general design principles, not evidence about how completely these protections operated in this trial. The registry gives the masking category as quadruple but does not identify the roles masked or describe procedures for maintaining masking.

The study summary describes participants with PTSD and AUD, selected genotypes at gamma-amino butyric acid transporter and receptor genes, and a sample of African-Americans including both genders and people with different types of trauma. It states that pregabalin was administered orally for 12 weeks. The primary-outcome population consisted of 44 participants who took at least 1 dose of study medication, with 26 in the experimental condition and 18 in the placebo condition. The registry does not report why this analysis population differs from the enrollment count, or whether participants were excluded for reasons other than taking no dose.

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: N=152 signed consent. Of these, 57 were randomized: 32 to pregabalin, 25 to placebo. 94 were not randomized: 1) did not meet alcohol use disorder criteria; 2) did not meet criteria for PTSD or other trauma disorder; 3) did not meet other eligibility criteria.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 44 took at least 1 dose of study medication: 26 in the experimental condition and 18 in the placebo condition. This is the analysis population. For some outcomes, there was missing data at the 12-week assessment.

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 Heavy Drinking Days as Measured by the Time Line Follow Back (TLFB), measured over 12 weeks.

The primary endpoint is heavy drinking days, measured in days using the Time Line Follow Back (TLFB). The registry says the measure is derived from an interview about the last 7 days and gives a 12-week timeframe. It characterizes the outcome as a mean of a continuous measure, with standard deviation as the dispersion measure. The record does not specify whether the 12-week assessment refers to a particular visit window or how incomplete TLFB interviews were handled.

As a general measurement concept, counting heavy drinking days focuses on the frequency of days meeting the study’s definition of heavy drinking, rather than on a single overall judgment about drinking. A mean can describe the average number of such days in a group, while a standard deviation describes how varied participant values are around that average. The registry record does not include the operational threshold used to classify a day as heavy drinking, so that definition should not be inferred.

The outcome is relevant to the stated objective of reducing risky drinking, but it does not alone capture every aspect of alcohol use or PTSD symptoms. Although the summary names PTSD symptoms as part of the primary objective, the registered primary outcome is heavy drinking days. The registry record does not provide a numerical mean, standard deviation, treatment contrast, confidence interval, or significance test for this endpoint. It also notes missing data at the 12-week assessment for some outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the mean describe?

The registry identifies heavy drinking days as a continuous outcome summarized by a mean and standard deviation. In general, the mean is the arithmetic average of observed values and gives a measure of the group’s central level. The standard deviation describes variability among individual values around that mean. Reporting both can help distinguish a group with a similar average but more varied participant responses from one with more closely clustered values. Neither measure reveals the full shape of the outcome distribution.

The registry record does not report the actual means or standard deviations for the treatment groups. It also does not report a numerical difference between groups. Consequently, no estimate of the treatment contrast can be interpreted from the posted primary-outcome entry. Although the record lists three outcome measures and three analyses, it does not describe the other outcomes or the analysis specifications in the information.

What would a treatment comparison mean?

In general, a treatment comparison estimates how the outcome differs between participants assigned to the intervention and those assigned to the comparator. Randomization supports a causal interpretation when the comparison follows the randomized groups and the assumptions of the analysis are reasonable. The registry labels the study randomized, but the reported primary-outcome population is defined as people who took at least 1 dose of study medication. The record does not say whether the primary analysis followed original assignment regardless of treatment received, or whether it used another approach. That distinction matters because analyses based on post-randomization participation can differ from analyses that preserve the original randomized groups.

A confidence interval is a statistical range that communicates uncertainty around an estimate under the model and assumptions used. It helps readers assess the precision and the range of effects reasonably compatible with the data. A p-value addresses compatibility with a specified null hypothesis under a statistical model; it does not measure the probability that a treatment is effective or the size of an effect. The registry record reports neither a confidence interval nor a p-value for the primary outcome, so those aspects of the comparison cannot be assessed.

How should the factorial classification be read?

The registry calls the trial factorial and describes treatment groups within two genotype categories: NI/I/II type and NI/NI type. In general, a factorial design can evaluate more than one factor and may support estimates of separate factor effects and their interaction. An interaction asks whether the treatment contrast differs across levels of another factor. This is a general explanation, not a claim that a particular interaction model was used. The record does not report the model, the prespecified contrasts, the genotype classification procedure, or any interaction estimate. A reader should not infer a genotype-specific treatment effect from the fact that genotype groups are listed.

Likewise, the masking classification is quadruple, but the registry does not specify which people were masked or how masking was maintained. Randomization and masking are design features that can reduce particular sources of bias; they do not guarantee that bias was absent or that groups were otherwise identical. Details about allocation concealment, deviations from assigned treatment, and adherence are not reported in the registry record.

Why can variation matter?

As a general statistical concept, continuous outcomes can vary substantially between participants. If the spread is greater than a model assumes, standard errors and confidence intervals based on that model may be inaccurate; this is one reason analysts assess distributional assumptions and choose methods appropriate to the observed data. Over-dispersion is commonly discussed for count outcomes when their variability exceeds that expected under a simple count model. Heavy drinking days are described as a mean of a continuous measure, but the registry does not state that a count model or any particular distributional model was used. There is no basis in the record for asserting that over-dispersion was present or for naming a method used to address it.

Missing observations can also affect precision and interpretation. The registry notes missing data at the 12-week assessment for some outcomes, but does not give the amount of missingness for heavy drinking days, its reasons, or the method used to handle it. General approaches to missing data rely on assumptions about why observations are missing. Different assumptions can lead to different estimates, so an analysis description and sensitivity checks are useful for evaluating robustness. Neither is reported in the registry record.

What can planning calculations establish?

In general, a sample-size calculation estimates how many participants an analysis may require under stated assumptions about variability, effect size, significance level, allocation, and desired power. Such a calculation is a planning illustration, not an observed finding and not evidence that a completed study had a particular probability of detecting an effect. The registry’s stated sample-size assumptions describe an illustration based on the observed effect, with two-sided significance level 0.05, equal allocation, and a normal approximation; the effect to detect is described as a fraction of the observed effect. The record does not give a sample-size justification for the original trial design. It also does not report a resulting required sample size in the information. Any planning illustration should therefore be distinguished from the trial’s observed enrollment and analysis population.

The registry does not report the primary statistical model, covariate adjustments, handling of repeated measures, test sidedness for the actual outcome analysis, or any interim-analysis plan. These details are not recoverable from the design label, outcome type, or sample-size assumptions. No particular method should be attributed to the investigators without a registry description.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and three analyses, but does not report their individual definitions or the statistical plan connecting them. It does not state which tests were primary or secondary beyond identifying heavy drinking days as the primary outcome, nor whether any adjustment for multiple testing was planned or performed. When multiple outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase; multiplicity procedures are sometimes used to address this concern. This is a general principle, not evidence that such a procedure was used in this trial. A multiplicity plan is not reported in the registry record.

The primary-outcome description states that 44 participants who took at least 1 dose were included: 26 in the experimental condition and 18 in the placebo condition. Enrollment was 57. The registry does not explain the difference between these counts, report the number randomized to each condition, or state whether the analysis population was defined before or after outcomes were observed. It also does not report whether participants were analyzed according to randomized assignment, treatment received, or another rule.

For some outcomes, the registry notes missing data at the 12-week assessment. It does not report the amount or pattern of missingness for the primary endpoint, the reasons observations were missing, or the method used to address missing values. General methods may rely on assumptions about the relationship between missingness and observed or unobserved outcomes; sensitivity analyses can show whether conclusions depend on those assumptions. The registry record does not describe a missing-data method or sensitivity analysis. These gaps limit assessment of whether the reported analysis population and available outcomes represent all randomized participants or whether missingness could have affected the comparison.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hospitalization (5.6%).

The registry lists one participant with a serious adverse event among 26 at risk in the pregabalin plus BBCET group, and one among 18 at risk in the placebo plus BBCET group. It reports zero deaths in both groups. For other adverse events, the registry lists 26 affected among 26 at risk in the pregabalin plus BBCET group and 18 affected among 18 at risk in the placebo plus BBCET group. These are descriptive registry counts; the record does not give event-level details or a statistical comparison.

Hospitalization is listed as a top serious-event term at 5.6%. The registry record does not report the denominator or additional detail needed to interpret that percentage, such as whether it refers to participants or events. It should not be treated as a separately established rate for either treatment group on the information available.

In general, adverse-event counts depend on how events were defined, collected, coded, and attributed. The registry does not report those details here, nor does it provide timing, duration, severity beyond the serious-event classification, or investigator attribution. The counts therefore describe the posted entries but do not establish why an event occurred or provide a complete comparative safety analysis. The study’s stated safety objective is to assess safety and tolerability; the registry entries alone do not resolve that objective.

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

The registry record establishes that a completed randomized, quadruple-masked, factorial phase 3 study examined pregabalin plus BBCET versus placebo plus BBCET among participants with PTSD, AUD, and selected genotypes. It identifies heavy drinking days measured by TLFB at 12 weeks as the primary outcome and describes the primary-outcome analysis population as 44 people who took at least 1 dose. These details clarify the question and the population represented in the stated primary analysis.

The record does not report the numerical primary-outcome results. It therefore does not show the mean number of heavy drinking days in either group, the size or direction of a treatment contrast, or the precision of that contrast. It also does not report a numerical result for PTSD symptoms, despite naming them in the study objective. The available registry information cannot establish whether pregabalin reduced risky drinking or PTSD symptoms, whether any effect differed by genotype, or whether an observed difference would be clinically important.

That limitation is about what can be concluded from this registry record, not a finding that the treatment had no effect. A completed status indicates trial status, not the direction or strength of an outcome. Likewise, the listed safety counts do not amount to proof of equivalent safety or of a treatment-related harm. Interpreting those issues would require fuller results and definitions.

As a general principle, an estimated effect and its uncertainty should be considered together. A numerical estimate describes the observed contrast, while an interval indicates how precisely it was estimated under the analysis assumptions. A significance test alone would not describe clinical importance; a non-significant result would not establish equivalence, and a statistically significant result would not by itself establish meaningful benefit. Here, the registry does not report the estimate, interval, or test for the primary endpoint, so those distinctions cannot be applied to the study’s primary comparison.

13. Why This Trial Matters Statistically

This trial is statistically notable for combining a randomized medication comparison with genotype categories in a factorial design. That structure raises an important distinction between an overall treatment contrast and a treatment contrast within genotype groups. In general, subgroup effects require direct statistical comparison and adequate precision; observing separate group results is not, by itself, evidence that effects differ. The registry lists NI/I/II type and NI/NI type groups but does not report genotype-specific estimates or an interaction analysis.

The primary outcome is also a continuous measure based on a recent recall period: heavy drinking days from TLFB data for the last 7 days at the 12-week timeframe. Its interpretation depends on how the measure was defined and analyzed, including the treatment of missing assessments. The registry identifies a mean and standard deviation but does not provide the endpoint values or the analysis method. This makes the trial’s statistical question clear while leaving its estimated answer unavailable in the registry record.

Another issue is the distinction between enrollment and the stated primary-outcome analysis population. The record reports enrollment of 57 and an analysis population of 44 who took at least 1 dose. Transparent reporting of how those populations relate is important because exclusions after randomization can affect the interpretation of a randomized comparison. The reasons and analysis strategy are not reported in the registry record.

The trial’s posted information therefore illustrates why design labels alone are not enough for statistical interpretation. Randomization, masking, and factorial structure describe important features, but conclusions also require outcome estimates, uncertainty, analysis populations, missing-data methods, and planned comparisons. Those details are not reported for the primary outcome in this record.

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.

The main trial-specific limitation for interpreting the posted primary outcome is that its numerical results are not reported in the registry record. There is no group mean, standard deviation, treatment contrast, confidence interval, or p-value for heavy drinking days. This prevents evaluation of the observed effect’s direction, magnitude, and precision.

The registry states that the primary-outcome analysis population comprised 44 participants who took at least 1 dose, while enrollment was 57. It does not explain the difference, report the randomized group counts, or describe whether the analysis followed assigned treatment. The record also notes missing data at the 12-week assessment for some outcomes but does not specify the amount or handling of missingness for heavy drinking days. These omissions make it difficult to assess how the analyzed participants and available outcomes relate to the randomized trial population.

Although the study is classified as factorial and describes two genotype categories, the registry does not report the planned comparisons, genotype-specific results, or an interaction test. It also does not report the operational definition of a heavy drinking day or numerical PTSD-symptom results. The stated primary objective is broader than the single primary outcome described in the record.

The safety entries lack event-level detail, timing, attribution, and a clearly stated denominator for the hospitalization percentage. The statistical model, covariate adjustments, multiplicity strategy, missing-data approach, and interim-analysis plan are not reported in the registry record. These limitations do not show that the analyses were inadequate; they identify information unavailable for evaluating them from the registry entry.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacogenetic Treatment With Anti-Glutaminergic Agents for Comorbid PTSD & AUD — NCT02884908.
• Registry record last updated 2024-03-13; status last verified 2024-02.
• Results first posted 2024-03-13.
• 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.

18. Record Summary

NCT02884908 is a completed randomized, quadruple-masked, factorial phase 3 trial sponsored by the University of Maryland, Baltimore. Enrollment was 57; the recorded start date was 2017-07-07 and the primary completion date was 2022-01-19.

The study compared oral pregabalin plus BBCET with placebo plus BBCET among participants with PTSD, AUD, and selected genotypes. The primary outcome was heavy drinking days measured with TLFB for the last 7 days at the 12-week timeframe. The stated analysis population included 44 participants who took at least 1 dose: 26 in the experimental condition and 18 in the placebo condition.

The registry record does not report numerical results for the primary outcome, the statistical comparison, or the method used to handle missing data. Safety entries list one serious adverse event in each group and zero deaths in both groups. These entries do not include the detail needed for a full comparative assessment.