Alcoholism: Developing Drugs for Treatment
4164-01-P CDER
2015-07-23 2015-04-14 2015-04-14
FDA-2015-D-0152-0007 FDA-2015-D-0152-0004 FDA-2015-D-0152-0003
04:00:00 04:00:00 04:00:00
https://api.regulations.gov/v4/comments/FDA-2015-D-0152-0007 https://api.regulations.gov/v4/comments/FDA-2015-D-0152-0004 https://api.regulations.gov/v4/comments/FDA-2015-D-0152-0003
Anonymous Anonymous Anonymous
Anonymous Anonymous Anonymous
I have been a psychiatrist for 25 years. Prior to the article in The Atlantic, April 2015, I had never heard of The Sinclair Method. I have watched the movie One Little Pill.Please, please consider The Sinclair Method of using naltrexone to reduce  the number of heavy drinking days.It is the same paradigm as Chantix.  With Chantix people smoke but they dont get the nicotine buzz so they are statistically more likely to give up smoking.With The Sinclair Method they drink but are statistically more likely to give up drinking.Will Finland be the only country to really look at this?Thank you,Jean J. Dansereau, M.D. Dear Food and Drug Administration:RE: Alcoholism: Developing Drugs for Treatment; Draft Guidance for Industry; AvailabilityAnthem agrees there is a strong need for additional pharmacologic treatments for alcoholism and applauds the Agencys commitment to examining this important issue. However, we have fundamental concerns relating to the draft guidance, namely, the shift in therapeutic endpoint for the treatment of alcohol use disorders. Our particular concern is that endpoints based on patterns of drinking be considered appropriate measures of clinical benefit. Unlike abstinence, the clinical and social implications of reduced-use remains unproven, with major potential consequences should the Agency shift accepted study endpoints. Anthem is aware that the concept of reduced use is a clinically useful endpoint in other substance use disorders. For example: reduced smoking associated with varenicline (Chantix) leads to quitting in some (Ebbert et al, JAMA 2015; 313:687-694); however, the value of reduced smoking is more certain at this time than reduced drinking or reduction in use of other illicit substances.  Absence of alcohol and drug use (abstinence) remains an important endpoint for members, families, and others. For example, members with alcohol use disorder and employed in the transportation industry as operators of vehicles are expected to remain abstinent from alcohol and illicit drugs to retain employment and for public safety.  Likewise, medical professionals, policeman and fireman with alcohol use disorders are expected to sustain abstinence for similar reasons. Social implications resulting from reduced alcohol and substance use (vs. abstinence) also remain largely unknown and poorly elucidated based on current data. Anthem suggests that the critical concept is trial endpoints (page 4, lines 155 and 156). The varenicline trial indicates that there appear to be trial designs that make abstinence and reduced drinking meaningful and feasible endpoints within the same trial and, at least potentially, as part of clinical practice.The shift in the Agencys use of clinically useful endpoints for alcohol use disorders is analogous to the Agencys accepted use of imaging-based disease free progression as an outcome for terminal malignancies. This paradigm shift occurred even though there was a paucity of data  demonstrating that imaging-based endpoints represented a clinically significant outcome for the patient; a shift, we should note, that remains incompletely supported by subsequent data. Before the Agency adopts a shift in its approach to evaluating the therapeutic endpoint for the treatment of alcohol use disorders, Anthem recommends that the Agency more fully assess the significance of clinical and social outcomes of reduced alcohol use and related outcomes for clinical and social impact as compared to the generally accepted measure of abstinence.  As a clinical researcher in addictions, I applaud your change in broadening the definition of successful treatments for substance use disorders. The notion of total abstinence as the best and only marker of a successful outcome was always arbitrary and not consistent with empirical research.With respect to medications specifically, the primary outcome of RCTs of naltrexone has always been the reduction of heavy drinking. And with reduced heavy drinking comes a concomitant reduction in alcohol related problems. And alcohol-related problems are the primary reasons heavy drinkers decide to change their drinking. So your expansion of the definition of a successful outcome can not only encourage research into new medications but also encourage many heavy drinkers to consider changing their drinking if success is not considered a yes/no proposition (e.g., abstinence or failure).