title: Results of a double-blind, placebo-controlled pharmacotherapy trial in alcoholism conducted in Germany and comparison with the US COMBINE study.
abstract: The results of placebo-controlled trials (RCTs) with acamprosate or naltrexone vary substantially. Those differences have been attributed to differing patient characteristics, recruitment strategies, treatment settings and remuneration systems. We tested these assumptions by comparing a new double-blind, placebo-controlled randomized trial conducted in Germany (called PREDICT Study) with data from the US COMBINE Study. PREDICT was designed according to the protocol of the COMBINE Study. A total of 426 alcohol-dependent patients were compared to 459 COMBINE Study patients corresponding to the treatment cells in PREDICT. All patients received acamprosate, naltrexone or placebo for 3 months (PREDICT) or 4 months (COMBINE). Biweekly manualized 'medical management' to enhance compliance was delivered in both studies. Time until the first occurrence of heavy drinking was the main outcome measure. PREDICT found neither acamprosate nor naltrexone to supply any additional benefit compared with placebo, which is at variance with a positive naltrexone effect being reported in the COMBINE Study. A secondary comparison between both studies showed better overall treatment outcomes in PREDICT, although these patients had been more severely affected than their COMBINE counterparts. The divergence in results may be attributable to basic differences in the treatment environments (such as in-patient pre-treatment versus primary outpatient care). We suggest that identically designed RCTs conducted in different parts of the world may help improve the external validity of RCTs. This approach could be called 'comparative efficacy research'.
authors.affiliation: Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
authors.forename: Tagrid
authors.initials: T
authors.lastname: Lemenager
authors.forename: Sabine
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Iris
authors.initials: I
authors.lastname: Reinhard
authors.forename: Derik
authors.initials: D
authors.lastname: Hermann
authors.forename: Anil
authors.initials: A
authors.lastname: Batra
authors.forename: Michael
authors.initials: M
authors.lastname: Berner
authors.forename: Norbert
authors.initials: N
authors.lastname: Wodarz
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.forename: Michael N
authors.initials: MN
authors.lastname: Smolka
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Zimmermann
authors.forename: Stefan
authors.initials: S
authors.lastname: Wellek
authors.forename: Falk
authors.initials: F
authors.lastname: Kiefer
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Anton
mesh_terms: D000077443:Acamprosate; D000328:Adult; D000427:Alcohol Deterrents / Q000008:administration & dosage / Q000627:therapeutic use*; D000437:Alcoholism / Q000188:drug therapy*; D000553:Ambulatory Care / Q000706:statistics & numerical data; D003376:Counseling; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D005858:Germany; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D010353:Patient Education as Topic; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States; D016903:Drug Monitoring
chemical_list: D000427:Alcohol Deterrents; D009292:Narcotic Antagonists; D010919:Placebos; D013654:Taurine; D009271:Naltrexone; D000077443:Acamprosate