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Background: Alcohol use disorder (AUD) is underdiagnosed and undertreated in medical settings, in part due to a lack of AUD assessment instruments that are reliable and practical for use in routine care. This study evaluates the test‐retest reliability of a patient‐report Alcohol Symptom Checklist questionnaire when it is used in routine care, including primary care and mental health specialty settings. Methods: We performed a pragmatic test‐retest reliability study using electronic health record (EHR) data from Kaiser Permanente Washington, an integrated health system in Washington state. The sample included 454 patients who reported high‐risk drinking on a behavioral health screen and completed two Alcohol Symptom Checklists 1 to 21 days apart. Subgroups of these patients who completed both checklists in primary care (n = 271) or mental health settings (n = 79) were also examined. The primary measure was an Alcohol Symptom Checklist on which patients self‐reported whether they experienced each of the 11 AUD criteria within the past year, as defined by the Diagnostic and Statistical Manual of Mental Disorders‐5th edition (DSM‐5). Results: Alcohol Symptom Checklists completed in routine care and documented in EHRs had excellent test‐retest reliability for measuring AUD criterion counts (ICC = 0.79, 95% CI: 0.76 to 0.82). Test‐retest reliability estimates were also high and not significantly different for the subsamples of patients who completed both checklists in primary care (ICC = 0.82, 95% CI: 0.77 to 0.85) or mental health settings (ICC = 0.74, 95% CI: 0.62 to 0.83). Test‐retest reliability was not moderated by having a past two‐year AUD diagnosis, nor by the age or sex of the patient completing it. Conclusions: Alcohol Symptom Checklists can reliably and pragmatically assess AUD criteria in routine care among patients who screen positive for high‐risk drinking. The Alcohol Symptom Checklist may be a valuable tool in supporting AUD‐related care and monitoring AUD criteria longitudinally in routine primary care and mental health settings. [ABSTRACT FROM AUTHOR]

Background: Recent research indicates some individuals who engage in heavy drinking following treatment for alcohol use disorder fare as well as those who abstain with respect to psychosocial functioning, employment, life satisfaction, and mental health. The current study evaluated whether these findings replicated in an independent sample and examined associations between recovery profiles and functioning up to 6 years later. Methods: Data were from the 3‐year and 7‐ to 9‐year follow‐ups of subsamples initially recruited for the COMBINE study (3‐year follow‐up: n = 694; 30.1% female, 21.0% non‐White; 7‐ to 9‐year follow‐up: n = 127; 38.9% female, 27.8% non‐White). Recovery at 3 years was defined by latent profile analyses including measures of health functioning, quality of life, employment, alcohol consumption, and cannabis and other drug use. Functioning at the 7‐ to 9‐year follow‐up was assessed using single items of self‐rated general health, hospitalizations, and alcohol consumption. Results: We identified 4 profiles at the 3‐year follow‐up: (i) low‐functioning frequent heavy drinkers (13.9%), (ii) low‐functioning infrequent heavy drinkers (15.8%), (iii) high‐functioning heavy drinkers (19.4%), and (iv) high‐functioning infrequent drinkers (50.9%). At the 7‐ to 9‐year follow‐up, the 2 high‐functioning profiles had the best self‐rated health, and the high‐functioning heavy drinking profile had significantly fewer hospitalizations than the low‐functioning frequent heavy drinking profile. Conclusions: Previous findings showing heterogeneity in recovery outcomes were replicated. Most treatment recipients functioned well for years after treatment, and a subset who achieved stable recovery engaged in heavy drinking and reported good health outcomes up to 9 years after treatment. Results question the long‐standing emphasis on drinking practices as a primary outcome, as well as abstinence as a recovery criterion in epidemiologic and treatment outcome research and among stakeholder groups and funding/regulatory agencies. Findings support an expanded recovery research agenda that considers drinking patterns, health, life satisfaction, and functioning. [ABSTRACT FROM AUTHOR]

Background: Abstinence and no heavy drinking days are currently the only Food and Drug Administration–approved end points in clinical trials for alcohol use disorder (AUD). Many individuals who fail to meet these criteria may substantially reduce their drinking during treatment, and most individuals with AUD prefer drinking reduction goals. One‐ and two‐level reductions in World Health Organization (WHO) drinking risk levels have been proposed as alternative end points that reflect reduced drinking and are associated with reductions in drinking consequences, improvements in mental health, and reduced risk of developing alcohol dependence. The current study examined the association between WHO drinking risk level reductions and improvements in physical health and quality of life in a sample of individuals with alcohol dependence. Methods: Secondary data analysis of individuals with alcohol dependence (n = 1,142) enrolled in the longitudinal, prospective COMBINE study, a multi site randomized placebo‐controlled clinical trial, examining the association between reductions in WHO drinking risk levels and change in blood pressure, liver enzyme levels, and self‐reported quality of life following treatment for alcohol dependence. Results: One‐ and two‐level reductions in WHO drinking risk level during treatment were associated with significant reductions in systolic blood pressure (p < 0.001), improvements in liver enzyme levels (all p < 0.01), and significantly better quality of life (p < 0.001). Conclusions: One‐ and two‐level reductions in WHO drinking risk levels predicted significant improvements in markers of physical health and quality of life, suggesting that the WHO drinking risk level reduction could be a meaningful surrogate marker of improvements in how a person "feels and functions" following treatment for alcohol dependence. The WHO drinking risk levels could be useful in medical practice for identifying drinking reduction targets that correspond with clinically significant improvements in health and quality of life. At least 1‐ and 2‐level reductions in the World Health Organization (WHO) drinking risk levels by the end of treatment were associated with significant improvements at the end of treatment for physical health and quality of life outcomes. The WHO drinking risk level reductions capture considerable improvement in how patients feel and function in alcohol clinical trials. [ABSTRACT FROM AUTHOR]

Background: Craving and negative affect are distressing and commonly experienced during alcohol use disorder (AUD) treatment. Patients may assume that initiating abstinence will intensify their cravings and negative affect despite limited empirical data to support this assumption. This study extends and replicates, under improved methodological conditions, previous work that found reductions in daily craving associated with initiating abstinence. Methods: Seventy‐eight adults (80.8% male, 57.1% Caucasian) in a clinical trial testing prazosin for AUD provided daily reports of drinking, craving, and negative affect for up to 12 weeks (mean = 64.77 daily reports). Participants were classified into 3 subgroups based on whether and when they initiated 14 days of continuous abstinence, including (i) “abstinence initiators” who quit drinking during treatment (n = 17), (ii) “already abstainers” who were abstinent at the start of treatment (n = 20), and (iii) “continued drinkers” who never initiated abstinence (n = 41). The timing and degree of change in craving and negative affect were compared across these groups using multivariate growth curve modeling. Results: All participant subgroups reported gradual reductions in craving over the course of treatment, with “abstinence initiators” reporting additional sudden reductions in craving upon initiating abstinence from alcohol. “Continued drinkers” reported higher levels of craving than “already abstainers” throughout the full course of treatment. Negative affect followed a different pattern of change, with “abstinence initiators” experiencing gradual reductions in negative affect after initiating abstinence but no changes prior to or immediately upon initiating abstinence, and with “already abstainers” and “continued drinkers” experiencing no changes in negative affect over time. Conclusions: Initiating abstinence is associated with immediate reductions in craving, followed by gradual reductions in both craving and negative affect. Results provide insight into the timing and magnitude of changes in theoretically and clinically important variables and may help patients anticipate when to expect improvement in craving and negative effect. [ABSTRACT FROM AUTHOR]

Background Recently, the Food and Drug Administration ( FDA) proposed to expand the options for primary end points in the development of medications for alcohol use disorder to include either abstinence from alcohol or a nonabstinent outcome: no heavy drinking days (with a heavy drinking day defined as more than 3 drinks per day for women and more than 4 drinks per day for men [>3/>4 cutoff]). The FDA also suggested that 6 months would be the most appropriate length for a clinical trial to demonstrate the stability of this nonabstinent drinking outcome. However, few alcohol clinical trials have examined the stability of nonheavy drinking during and after treatment. Methods In a secondary analysis of the COMBINE study data ( n = 1,383), we examined transitions in heavy drinking days during the course of treatment (months 1 through 4), during the transition out of treatment (months 4 through 7), and up to 12 months afterward (months 13 through 16) using latent variable mixture models. Results Heavy drinking and nonheavy drinking were relatively stable in consecutive months (minimum agreement [kappa] = 0.64 for months 1 to 2). Most individuals were stable low-risk drinkers/abstainers or heavy drinkers by the end of treatment, as characterized by a 10% probability (or less) of transitioning out of either a no heavy drinking state or a heavy drinking state. More than two-thirds of the heavy drinkers who exceeded the heavy drinking threshold during treatment reported, on average, a 64% reduction in drinking frequency and a 38% reduction in drinking intensity from pretreatment drinking levels. Conclusions The results show stability of no heavy drinking as an outcome within the first 4 months of treatment and that the >3/>4 drink cutoff may mask substantial reductions in alcohol consumption among some patients. Future studies should explore the clinical utility of reduction end points. [ABSTRACT FROM AUTHOR]

Background Alcohol use disorder (AUD) is a highly prevalent public health problem associated with considerable individual and societal costs. Abstinence from alcohol is the most widely accepted target of treatment for AUD, but it severely limits treatment options and could deter individuals who prefer to reduce their drinking from seeking treatment. Clinical validation of reduced alcohol consumption as the primary outcome of alcohol clinical trials is critical for expanding treatment options. One potentially useful measure of alcohol treatment outcome is a reduction in the World Health Organization (WHO, International Guide for Monitoring Alcohol Consumption and Related Harm. Geneva, Switzerland, 2000) risk levels of alcohol use (very high risk, high risk, moderate risk, and low risk). For example, a 2-shift reduction in WHO risk levels (e.g., high risk to low risk) has been used by the European Medicines Agency (2010, Guideline on the Development of Medicinal Products for the Treatment of Alcohol Dependence. UK) to evaluate nalmefene as a treatment for alcohol dependence (AD; Mann et al. 2013, Biol Psychiatry 73, 706-13). Methods The current study was a secondary data analysis of the COMBINE study ( n = 1,383; Anton et al., ) to examine the association between reductions in WHO risk levels and reductions in alcohol-related consequences and mental health symptoms during and following treatment in patients with AD. Results Any reduction in WHO risk drinking level during treatment was associated with significantly fewer alcohol-related consequences and improved mental health at the end of treatment and for up to 1 year posttreatment. A greater reduction in WHO risk drinking level predicted a greater reduction in consequences and greater improvements in mental health. Conclusions Changes in WHO risk levels appear to be a valid end point for alcohol clinical trials. Based on the current findings, reductions in WHO risk drinking levels during treatment reflect meaningful reductions in alcohol-related consequences and improved functioning. [ABSTRACT FROM AUTHOR]

Background The construct of relapse is used widely in clinical research and practice of alcohol use disorder (AUD) treatment. The purpose of this study was to test the predictive validity of commonly appearing definitions of AUD relapse in the empirical literature. Methods Secondary analyses of data from Project MATCH and COMBINE were conducted using 7 definitions of 'relapse' based on drinking quantity within a single drinking episode: any drinking; at least 4/5 drinks for women/men; at least 4.3/7.1 drinks for women/men; at least 6/7 drinks for women/men; at least 6 drinks; at least 7/9 drinks for women/men; and at least 8/10 drinks for women/men. Relapse was used to predict alcohol consumption, related consequences, and nonconsumption outcomes (quality of life, psychosocial functioning) at the end of treatment and up to 1 year posttreatment. Results Regression analyses indicated within-treatment relapse definitions significantly predicted end-of-treatment alcohol consumption and alcohol-related consequences. Heavy drinking definitions were generally more predictive than the any drinking definition, but no single heavy drinking definition was consistently a better predictor of outcomes. Relapse definitions were less predictive of longer-term alcohol-related outcomes and both shorter- and longer-term nonconsumption outcomes, including health and psychosocial functioning. Conclusions One particular definition of relapse did not consistently stand out as the best predictor. Advances in AUD research may require reconceptualization of relapse as a multifaceted dynamic process and may consider a wider range of relevant behaviors (e.g., health and psychosocial functioning) when examining the change process in individuals with AUD. [ABSTRACT FROM AUTHOR]

Background: Missing data are common in alcohol clinical trials for both continuous and binary end points. Approaches to handle missing data have been explored for continuous outcomes, yet no studies have compared missing data approaches for binary outcomes (e.g., abstinence, no heavy drinking days). This study compares approaches to modeling binary outcomes with missing data in the COMBINE study. Methods: We included participants in the COMBINE study who had complete drinking data during treatment and who were assigned to active medication or placebo conditions (N = 1,146). Using simulation methods, missing data were introduced under common scenarios with varying sample sizes and amounts of missing data. Logistic regression was used to estimate the effect of naltrexone (vs. placebo) in predicting any drinking and any heavy drinking outcomes at the end of treatment using 4 analytic approaches: complete case analysis (CCA), last observation carried forward (LOCF), the worst case scenario (WCS) of missing equals any drinking or heavy drinking, and multiple imputation (MI). In separate analyses, these approaches were compared when drinking data were manually deleted for those participants who discontinued treatment but continued to provide drinking data. Results: WCS produced the greatest amount of bias in treatment effect estimates. MI usually yielded less biased estimates than WCS and CCA in the simulated data and performed considerably better than LOCF when estimating treatment effects among individuals who discontinued treatment. Conclusions: Missing data can introduce bias in treatment effect estimates in alcohol clinical trials. Researchers should utilize modern missing data methods, including MI, and avoid WCS and CCA when analyzing binary alcohol clinical trial outcomes. [ABSTRACT FROM AUTHOR]