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Alcohol Clinical Trials Initiative (ACTIVE)

The mission of the Alcohol Clinical Trials Initiative (ACTIVE) workgroup is to develop consensus reviews and recommendations to improve the design, execution, and interpretation of trials of medications for the treatment of alcohol dependence. It is not the intention of the group to propose standards that would be considered as requirements for the approval of product applications by regulatory agencies, but to advance the science of clinical trials in alcoholism treatment. Although the primary interest at this time is in studies of medications to treat alcohol dependence, the recommendations of this group may also apply to non-drug treatments. The processes that lead to consensus reviews and recommendations in this area might be applied to the development of consensus reviews and recommendations for trials to treat other drug dependencies. In addition, the ASCP leadership believes ACTIVE could be a "model" for other industry, academic and government agencies initiatives.  The ACTIVE Workgroup is made up of two representatives from each of the supporting corporations, representatives from FDA,  NIDA and a number of academic experts, as well as consultation with NIAAA on an ad hoc basis. ACTIVE also includes academic experts from Europe and exchanges information with the European Medications Agency (EMA) on an ad hoc basis. The twice a year meetings began in January 2009 and are ongoing.

 

 

Current Supporters:

  • Indivior
  • Kinnov Therapeutics

Past Supporters:

  • Abbott/Abbvie
  • Amygdala Neurosciences, Inc.
  • Alkermes
  • Arbor Pharmaceuticals
  • Dicerna
  • Eli Lilly & Company
  • Ethypharm
  • GlaxoSmithKline
  • Indivior
  • Janssen
  • Lilly
  • Lundbeck
  • Mitsubishi Tanabe Pharma
  • Otsuka
  • Pear Therapeutics
  • Pfizer
  • Schering Plough

 

ACTIVE Scientific Meeting Presentations:

ACTIVE Published and In-Press Papers

    • Aldridge AP, Zarkin GA, Dowd WN, Witkiewitz K, Hasin DS, O'Malley SS, Isenberg K, Anton RF. The Relationship Between Reductions in WHO Risk Drinking Levels During Treatment and Subsequent Healthcare Costs for the ACTIVE Workgroup. J Addict Med. 2021 Dec 3. doi: 10.1097/ADM.0000000000000925. Epub ahead of print. PMID: 34864785.
    • Witkiewitz K, Kranzler H, Hallgren K, Hasin D, Aldridge A, Zarkin G, Mann K, O’Malley S, and Anton RF. Stability of Drinking Reductions and Long-term Functioning Among Patients with Alcohol Use Disorder. Journal of General Internal Medicine. 2021 Feb; 36(2):404-412. PubMed PMID: 33180306; PubMed Central PMCID: PMC7878601.
    • Shmulewitz D, Aharonovich E,Witkiewitz K, Raymond RF, Kranzler HR, Scodes J, Mann KF, Wall MM, Hasin D.  The World Health Organization Risk Drinking Levels Measure of Alcohol Consumption: Prevalence and Health Correlates in US Adult Nationally Representative Surveys, 2001-2002 and 2012-2013. American Journal of Psychiatry. 2021 Jan 21. PubMed PMID: 33472388.
    • Witkiewitz K, Heather N, Falk DE, Litten RZ, Hasin DS, Kranzler HR, Mann KF, O'Malley SS, Anton RF. World Health Organization risk drinking level reductions are associated with improved functioning and are sustained among patients with mild, moderate and severe alcohol dependence in clinical trials in the United States and United Kingdom. 2020 Sep;115(9):1668-1680. doi: 10.1111/add.15011. Epub 2020 Mar 10. PMID: 32056311; PMCID: PMC7841874.
    • Knox J, Scodes J, Witkiewitz K, Kranzler H, Mann K, O’Malley S, Wall M, Anton R, Hasin D, ACTIVE Group. Reduction in World Health Organization (WHO) Risk Drinking Levels and Cardiovascular Disease. Alcohol Clinical and Experimental Research. 2020 Aug; 44(8):1625-1635. PubMed PMID: 32619058; PubMed Central PMCID: PMC7484295.
    • Anton RF, Witkiewitz K, Falk D, Litten R, Hasin D, Mann K, O’Malley SS., Response to Dr. Mark Litt Commentary. Alcohol Clinical and Experimental Research. 2019 Aug 5. PubMed PMID: 31381170.
    • Witkiewitz K, Falk DE, Litten RZ, Hasin DS, Kranzler HR, Mann KF, O’Malley SS, Anton RF. Maintenance of World Health Organization Risk Drinking Level Reductions and Posttreatment Functioning Following a Large Alcohol Use Disorder Clinical Trial. Alcoholism: Clinical and Experimental Research. 2019 May; 43(5): 979-987. PubMed PMID: 30951210; PubMed Central PMCID: PMC6502682.
    • Knox J, Wall M, Witkiewitz K, Kranzler HR, Falk DE, Litten R, Mann K, O’Malley SS,  Scodes J, Anton R, Hasin DS. Reduction in Non-abstinent World Health Organization (WHO) Drinking risk Levels and Drug Use Disorders: 3-year Follow-up Results in the US General Population. Drug Alcohol Depend. 2019 Apr 1; 197: 228-235. PubMed PMID: 30852375; PubMed Central PMCID: PMC440807.
    • Falk DE, O’Malley SS, Witkiewitz K, Anton RF, Litten RZ, Slater M, Kranzler HR, Mann KF, Hasin DF, Johnson B, Meulien D, Ryan M, & Fertig J. Evaluation of Drinking Risk Levels as Outcomes in Alcohol Pharmacotherapy Trials: A Secondary Analysis of 3 Randomized Clinical Trials. JAMA Psychiatry. 2019 March 13. PubMed PMID: 30865232l; PubMed PMCID: PMC6450273.
    • Knox J, Scodes J, Wall M, Witkiewitz K, Kranzler HR, Falk DE, Litten RZ, Mann KF, O'Malley SS, Anton RF, Hasin DS; Alcohol Clinical Trials (ACTIVE) Workgroup. Reduction in non-abstinent WHO drinking risk levels and depression/anxiety disorders: 3-year follow-up results in the US general population. ­Drug Alcohol Depend. 2019 Feb 14; 197:228-235. PubMed PMID: 30852375.
    • Witkiewitz K, Kranzler HR, Hallgren KA, Hasin DE, Mann KF, Falk DE, Litten RZ, O’Malley SS, & Anton RF. Drinking Risk Level Reductions Associated with Improvements in Physical Health and Quality of Life Among Individuals with Alcohol Use Disorder. Alcoholism: Clinical and Experimental Research. 2018 Dec; 42(12):2453-2465. PubMed PMID: 30395350; PubMed Central PMCID: PMC6286196.
    • Knox J, Wall M, Witkiewitz K, Kranzler HR, Falk DE, Litten RZ, Mann KF, O’Malley SS, Scodes J, Anton RF, & Hasin DS. Reduction in Non-Abstinent WHO Drinking Risk Levels and Change in Risk for Liver Disease and Positive AUDIT-C Scores: Prospective 3-Year Follow-Up Results in the US General Population. Alcoholism: Clinical and Experimental Research. 2018 Nov; 42(11)2256-2265. PubMed PMID: 30204248; PubMed Central PMCID: PMC6263142.
    • Mann K, Aubin HJ, Charlet K, & Witkiewitz K. Can Reduced Drinking be a Viable Goal for Alcohol Dependent Patients? World Psychiatry. 2017 Oct; 16(3):325-326. PubMed PMID: 28941117; PubMed Central PMCID: PMC5608854.
    • Mann K, Aubin HJ, & Witkiewitz K. Reduced Drinking in Alcohol Dependence Treatment, What is the Evidence? European Addiction Research. 2017 Sep 22;23(5):219-230. PubMed PMID: 28934736.
    • Litten RZ, Falk DE, O’Malley SS, Witkiewitz K, Mann KF, Anton RF. Letter to Editor in Response to Johnson’s Commentary (2017) on the Witkiewitz et al. (2017) Article. Alcoholism: Clinical and Experimental Research. 2017 May 4. PubMed PMID: 28471501.
    • Witkiewitz K, Wilson AD, Pearson MR, Hallgren KA, Falk DE, Litten RZ, Kranzler HR, Mann KR, Hasin DS, O'Malley SS, & Anton RF. Temporal Stability of Heavy Drinking Days and Drinking Reductions Among Heavy Drinkers in the COMBINE Study. Alcoholism: Clinical and Experimental Research. 2017 May;41(5):1054-1062. PubMed PMID: 28295414; PubMed Central PMCID: PMC5404970.
    • Hasin DS, Wall M, Witkiewitz K, Kranzler HR, Falk D, Litten RZ, Mann K, O’Malley SS, Scodes J, Robinson RL, Anton RF. Change in Non-Abstinent World Health Organization Risk Drinking Levels and Alcohol Dependence: A 3-Year Follow-Up Study in the United States General Population. Lancet Psychiatry. 2017 Jun; 4(6):469-476. PubMed PMID: 28456501.
    • Witkiewitz K, Hallgren KA, Kranzler HR, Mann KR, Hasin DS, Falk DE, Litten RZ, O'Malley SS, & Anton RF. Clinical Validation of Reduced Alcohol Consumption after Treatment for Alcohol Dependence using the World Health Organization Risk Drinking Levels. Alcoholism: Clinical and Experimental Research. 2017 Jan;41(1):179-186. PubMed PMID: 28019652; PubMed Central PMCID: PMC5205540.
    • Witkiewitz, K, Falk, DE, Kranzler HR, Litten RZ, Hallgren KA, O'Malley SS, & Anton RF. Missing Data in Alcohol Clinical Trials with Binary Outcomes. Alcoholism: Clinical and Experimental Research. 2016 Jul;40(7):1548-57. PubMed PMID: 27254113.
    • Witkiewitz K, Falk DE, Kranzler HR, Litten RZ, Hallgren KA, O'Malley SS, & Anton RF. Methods to analyze treatment effects in the presence of missing data for a continuous heavy drinking outcome measure when participants drop out from treatment in alcohol clinical trials. Alcoholism: Clinical and Experimental Research. 2014 Nov;38(11):2826-34. PubMed PMID: 25421518; PubMed Central PMCID: PMC4244651.
    • Stout RL, Braciszewski JM, Subbaraman MS, Kranzler HR, O'Malley SS, Falk D and ACTIVE group. What happens when people discontinue taking medications? Lessons from COMBINE. 2014 Dec; 109(12):2044-52. PubMed PMID: 25098969 PubMed Central PMCID: PMC4254710.
    • Falk DE, Litten RZ, Anton RF, Kranzler HR, Johnson BA, Active Workgroup. Cumulative proportion of responders analysis (CPRA) as a tool to assess treatment outcome in alcohol clinical trials. J Stud Alcohol Drugs. 2014 Mar;75(2):335-46. PubMed PMID: 24650828; PubMed Central PMCID: PMC3965687.
    • Greenfield TK, Ye Y, Bond J, Kerr WC, Nayak MB, Kaskutas LA, Anton RF, Litten RZ, Kranzler HR. Risks of alcohol use disorders related to drinking patterns in the US general population. J Stud Alcohol Drugs. 2014 Mar;75(2):319-27. PubMed PMID: 24650826; PubMed Central PMCID: PMC3965685.
    • Anton RF, Litten RZ, Falk DE, Palumbo JM, Bartus RT, Robinson RL, Kranzler HR, Kosten TR, Meyer RE, O'Brien CP, Mann K, Meulien D. The Alcohol Clinical Trials Initiative (ACTIVE): purpose and goals for assessing important and salient issues for medications development in alcohol use disorders. 2012 Jan;37(2):402-11. PubMed PMID: 21900883; PubMed Central PMCID: PMC3242301

    ACTIVE Posters:

    • Knox J. (2019, June). WHO Findings from the NESARC. Poster presented at the College on Problems of Drug Dependence 81st Annual Scientific Meeting, San Antonio, Texas.
    • O’Malley SS. (2018, June). Response to Pharmacotherapy: A Comparison of Endpoints Based on Abstinence, No Heavy Drinking and Reductions in WHO Drinking Levels in Three Trials. Poster presented at the Research Society on Alcoholism Scientific Meeting, San Diego, CA.
    • Hasin D. (2018, June). WHO-Defined Risk Drinking Levels and Drinking Consequences: Prospective Findings From the NESARC Waves 1 & 2 (2001-2005). Poster presented at the Research Society on Alcoholism Scientific Meeting, San Diego, CA.
    • Falk DE. (2017, December). Novel Efficacy Endpoints Based on Shifts in the World Health Organization (WHO) Risk Levels of Drinking: Treatment Effects in Alcohol Pharmacotherapy Trials. Poster presented at the American College of Neuropsychopharmacology 56th Annual Meeting, Palm Springs, CA.

     ACTIVE Data Presentations:

    • O’Malley S. (2021, June). WHO Risk Drinking Reduction A New Endpoint for Clinical Trials. Symposium presented at the Research Society on Alcoholism Scientific Meeting, Virtual.
    • Anton, R. (2021, June). WHO Risk Drinking Level: A Harm Reduction Outcome For Clinical Trials For Alcohol Use Disorder. Symposium presented at the Research Society on Alcoholism Scientific Meeting, Virtual.
    • Knox J. (presenter), Scodes J., Witkiewitz K., Kranzler H., Mann K., O’Malley S., Wall M., Anton R., Hasin D. (2021, June). Reduction in WHO Risk Drinking Levels and Cardiovascular Disease: 3-year Follow-up Results in the US General Population. Symposium presented at the Research Society on Alcoholism Scientific Meeting, Virtual.
    • Schacht J., Anton R. (2019, June). Prediction Of Alcohol Harm Reduction (Who RDL) Outcomes From Cue-Elicited Brain Activation In A Randomized Trial Of Naltrexone. Symposium presented at the Research Society on Alcoholism Scientific Meeting, Minneapolis, Minnesota.
    • Witkiewitz K. (2019, June). Beyond Abstinence: Reductions in Drinking as an Endpoint for Alcohol Clinical Trials. Symposium presented at the College on Problems of Drug Dependence 81st Annual Scientific Meeting, San Antonio, Texas.
    • Hasin D. (2019, June). Validation of a Measure of Opioid Use Disorder Among Chronic Pain Patients Treated With Opioids. Workshop presented at the College on Problems of Drug Dependence 81st Annual Scientific Meeting, San Antonio, Texas.
    • Anton RF. (2018, December) Harm Reduction as a Goal in AUD Pharmacotherapy– Role For the WHO Risk Drinking Category Change. Symposium presented at the AAAP Annual Meeting and Scientific Symposium, Bonita Springs, FL.
    • O’Malley SS. (2018, June) 2018 RSA Distinguished Researcher Awardee: Beyond Abstinence: An Evolving Perspective on Naltrexone and Pharmacotherapy for Alcohol Use Disorder. Plenary presented at the Research Society on Alcoholism Scientific Meeting, San Diego, CA.
    • Anton RF. (2018, June) Insights From The Design and Implementation of Medications Development Trials for Alcohol Use Disorder. Panel presented at the Research Society on Alcoholism Scientific Meeting, San Diego, CA.
    • O’Malley SS. (2018, May) ACTIVE Update: Reduction in World Health Organization (WHO) Drinking Risks Level as a Primary Endpoint for Alcohol Treatment Trials. Panel presented at the ASCP Annual Meeting, Miami Beach, Florida.
    • Witkiewitz K. (2017, August). Reduction in  World  Health  Organization  (WHO)  Drinking  Risk  Level  as  an  Endpoint  for  Alcohol  Clinical  Symposium presented at the APA Annual Meeting, Washington D.C.
    • O’Malley SS. (2017, May). The Development and Selected Performance of Patient Reported Outcomes (PRO) in Psychopharmacotherapy Trials – is the Juice Worth the Squeeze? A Review of Initiatives by the FDA, NIH, and the Alcohol Clinical Trials Initiative (ACTIVE). Panel presented at the ASCP Annual Meeting, Miami Beach, Florida.

     

    ACTIVE Press Coverage:

    • O’Connor, A. (2021, July 12). Alcohol Abuse Is on the Rise, but Doctors Too Often Fail to Treat It. The New York Times, Retrieved from https://www.nytimes.com/2021/07/12/well/live/alcohol-abuse-drinking-treatment.html?referringSource=articleShare