Dataset Information

Subgroup Identification in Personalized Treatment of Alcohol Dependence.

ABSTRACT: Identification of patient subgroups to enhance treatment effects is an important topic in personalized (or tailored) alcohol treatment. Recently, several recursive partitioning methods have been proposed to identify subgroups benefiting from treatment. These novel data mining methods help to address the limitations of traditional regression-based methods that focus on interactions.We propose an exploratory approach, using recursive partitioning methods, for example, interaction trees (IT) and virtual twins (VT), to flexibly identify subgroups in which the treatment effect is likely to be large. We apply these tree-based methods to a pharmacogenetic trial of ondansetron.Our methods identified several subgroups based on patients' genetic and other prognostic covariates. Among the 251 subjects with complete genotype information, the IT method identified 118 with specific genetic and other prognostic factors, resulting in a 17.2% decrease in the percentage of heavy drinking days (PHDD). The VT method identified 88 subjects with a 21.8% decrease in PHDD. Overall, the VT subgroup achieved a good balance between the treatment effect and the group size.A data mining approach is proposed as a valid exploratory method to identify a sufficiently large subgroup of subjects that is likely to receive benefit from treatment in an alcohol dependence pharmacotherapy trial. Our results provide new insights into the heterogeneous nature of alcohol dependence and could help clinicians to tailor treatment to the biological profile of individual patients, thereby achieving better treatment outcomes.

SUBMITTER: Hou J

PROVIDER: S-EPMC4491003 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Subgroup Identification in Personalized Treatment of Alcohol Dependence.

Hou Jue J Seneviratne Chamindi C Su Xiaogang X Taylor Jeremy J Johnson Bankole B Wang Xin-Qun XQ Zhang Heping H Kranzler Henry R HR Kang Joseph J Liu Lei L

Alcoholism, clinical and experimental research 20150529 7

<h4>Background</h4>Identification of patient subgroups to enhance treatment effects is an important topic in personalized (or tailored) alcohol treatment. Recently, several recursive partitioning methods have been proposed to identify subgroups benefiting from treatment. These novel data mining methods help to address the limitations of traditional regression-based methods that focus on interactions.<h4>Methods</h4>We propose an exploratory approach, using recursive partitioning methods, for exa ...[more]

PMID: 26031187

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Project description:BackgroundThe tradition of consuming alcohol has long been a part of Italian culture and is responsible for a large health burden. This burden may be reduced with effective interventions, one of the more important of which is treatment for Alcohol Dependence (AD). The aim of this article is to estimate the burden of disease in Italy attributable to alcohol consumption, heavy alcohol consumption, and AD. An additional aim of this paper is to examine the effects of increasing the coverage of treatment for AD on the alcohol-attributable burden of disease.MethodsAlcohol-attributable deaths and the effects of treatments for AD were estimated using alcohol-attributable fractions and simulations. Deaths, potential years of life lost, years lived with disability, and disability adjusted life years lost were obtained for 2004 for Italy and for the European Union from the Global Burden of Disease study. Alcohol consumption data were obtained from the Global Information System on Alcohol and Health. The prevalences of current drinkers, former drinkers, and lifetime abstainers were obtained from the GENder Alcohol and Culture International Study. The prevalence of AD was obtained from the World Mental Health Survey. Alcohol relative risks were obtained from various meta-analyses.Results5,320 deaths (1,530 female deaths; 3,790 male deaths) or 5.9% of all deaths (4.9% of all female deaths; 6.3% of all male deaths) of people 15 to 64 years of age were estimated to be alcohol-attributable. Of these deaths, 74.5% (61.3% for females; 79.8% for males) were attributable to heavy drinking, and 26.9% (25.6% for females; 27.5% for males) were attributable to AD. Increasing pharmacological AD treatment coverage to 40% would result in an estimated reduction of 3.3% (50 deaths/year) of all female and 7.6% (287 deaths/year) of all male alcohol-attributable deaths.ConclusionsAlcohol was responsible for a large proportion of the burden of disease in Italy in 2004. Increasing treatment coverage for AD in Italy could reduce that country's alcohol-attributable burden of disease.

Project description:ImportanceApproved medications for alcohol dependence are prescribed for less than 9% of US alcoholics.ObjectiveTo determine if gabapentin, a widely prescribed generic calcium channel/γ-aminobutyric acid-modulating medication, increases rates of sustained abstinence and no heavy drinking and decreases alcohol-related insomnia, dysphoria, and craving, in a dose-dependent manner.Design, participants and settingA 12-week, double-blind, placebo-controlled, randomized dose-ranging trial of 150 men and women older than 18 years with current alcohol dependence, conducted from 2004 through 2010 at a single-site, outpatient clinical research facility adjoining a general medical hospital.InterventionsOral gabapentin (dosages of 0 [placebo], 900 mg, or 1800 mg/d) and concomitant manual-guided counseling.Main outcomes and measuresRates of complete abstinence and no heavy drinking (coprimary) and changes in mood, sleep, and craving (secondary) over the 12-week study. RESULTS Gabapentin significantly improved the rates of abstinence and no heavy drinking. The abstinence rate was 4.1% (95% CI, 1.1%-13.7%) in the placebo group, 11.1% (95% CI, 5.2%-22.2%) in the 900-mg group, and 17.0% (95% CI, 8.9%-30.1%) in the 1800-mg group (P = .04 for linear dose effect; number needed to treat [NNT] = 8 for 1800 mg). The no heavy drinking rate was 22.5% (95% CI, 13.6%-37.2%) in the placebo group, 29.6% (95% CI, 19.1%-42.8%) in the 900-mg group, and 44.7% (95% CI, 31.4%-58.8%) in the 1800-mg group (P = .02 for linear dose effect; NNT = 5 for 1800 mg). Similar linear dose effects were obtained with measures of mood (F2 = 7.37; P = .001), sleep (F2 = 136; P < .001), and craving (F2 = 3.56; P = .03). There were no serious drug-related adverse events, and terminations owing to adverse events (9 of 150 participants), time in the study (mean [SD], 9.1 [3.8] weeks), and rate of study completion (85 of 150 participants) did not differ among groups.Conclusions and relevanceGabapentin (particularly the 1800-mg dosage) was effective in treating alcohol dependence and relapse-related symptoms of insomnia, dysphoria, and craving, with a favorable safety profile. Increased implementation of pharmacological treatment of alcohol dependence in primary care may be a major benefit of gabapentin as a treatment option for alcohol dependence.Trial registrationclinicaltrials.gov Identifier: NCT00391716.

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Subgroup Identification in Personalized Treatment of Alcohol Dependence.

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Subgroup Identification in Personalized Treatment of Alcohol Dependence.

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