Pharmacotherapy for the treatment of drug addiction has received far too little attention, despite the clinical success of methadone, which dates back to the 1960s. Over the last 30 years only two additional medications have been approved for the treatment of opiate addiction, naltrexone and levo-alpha-acetylmethadol (LAAM), and it is important to note that both of those medications were developed in the 1960s and early 1970s. There is no approved medication for the treatment of cocaine addiction. During the same 30 year period, serious medical and social problems have evolved as drug addiction has become a route for spreading AIDS through the sharing of contaminated needles and trading sex for drugs, multiple-drug-resistant tuberculosis has become common in immunocompromised HIV-infected drug users, an association between illicit drug use and increasing violent crime has become clear, and the medical consequences for infants of in utero exposure to cocaine has become evident.

It was in the climate of a near absence of private sector and government activity in the development of anti-addiction medications and a growing public health crisis that the Congress passed Public Law 100-690 in 1988, which established the Medications Development Division (MDD) in the National Institute on Drug Abuse (NIDA). The division began in 1990 to coordinate and encourage academic, private, and federal regulatory involvement in developing and bringing to market new medications for the treatment of drug addiction.

The ADAMHA Reorganization Act of July 1992 (Public Law 102-321) stipulated that the Department of Health and Human Services contract with the National Academy of Sciences to establish a committee of the Institute of Medicine (IOM) to examine the current environment for the development of anti-addiction medications. In response to the Congressional mandate, the Committee to Study Medication Development and Research at the National Institute on Drug Abuse was formed. The 14-member interdisciplinary IOM committee included persons with expertise in behavioral pharmacology, drug abuse treatment, neuroscience, drug development, health-care economics, clinical research, and federal regulatory law.

NIDA and IOM decided that a two-phase effort would most beneficially address the complex issues associated with the development of an anti-addiction medication. The committee was charged to

• Determine the extent to which current scientific knowledge limits the development of pharmacological treatments for drug addiction,
• Review the background and progress of the NIDA MDD since its inception in 1990,
• Consider the current role of the Food and Drug Administration (FDA) and other government entities in the process for approving
  anti-addiction medications,
• Survey the incentives and disincentives to private development of medications including government regulatory processes and the
  potential market for anti-addiction medications, and
• Determine the current role of the private sector in the development of medications for drug addiction.

The committee focused its attention exclusively on medications for treating opiate and cocaine addictions, because individuals with those addictions are disproportionately responsible for violent crimes and for the transmission of infectious diseases such as AIDS. The committee recognizes, however, that the two addictive drugs that are most important with respect to morbidity, mortality, and economic costs are alcohol and nicotine.

The committee formally met six times during the course of the entire study, in addition to holding a workshop, and meeting in smaller focus groups. From October 1993 through January 1994 the IOM committee met three times to examine the role of the Medications Development Division at NIDA and identify the disincentives to private sector development of anti-addiction medications specifically for the treatment of opiate and cocaine addictions. Additionally, the committee met with senior executives of pharmaceutical companies, representatives of federal agencies (the Drug Enforcement Administration, NIDA, the National Institutes of Health, and FDA), and the IOM Forum on Drug Development, as well as conducting a survey of the member companies of the Pharmaceutical Research and Manufacturers of America (formerly the Pharmaceutical Manufacturers Association), the Biotechnology Industry Organization (BIO), and the Generic Pharmaceutical Industry Association (GPIA). The committee issued its preliminary report, Development of Anti-Addiction Medications: Issues for the Government and Private Sector, in March 1994 which was disseminated to NIDA, ONDCP, various Congressional committees, other interested parties, and was the subject of a Senate Judiciary Committee hearing on April 19, 1994.

The committee held its final three meetings, from April 1994 through September 1994. During the second phase of its work, the committee:

• provided a more detailed examination of the issues identified in the preliminary report regarding disincentives to private sector development of anti-addiction medications,
• further assessed the market environment for developing those medications, and
• recommended policy and legislative solutions for overcoming the obstacles and disincentives for the development of anti-addiction medications.

The committee heard from a wide range of experts at their June 13, 1994 Workshop on Policies to Stimulate Private Sector Development of Anti-Addiction Medications; sessions focused on market issues, treatment financing, federal and state regulations regarding substance abuse research and treatment, and education and training (see Appendix F for workshop agenda and participant list). This report combines the two phases of the committee's work; the organization and content of the report are outlined in the Note to the Reader.

The committee, recognizing the medical consequences and socioeconomic problems associated with drug abuse and the dire need for development of anti-addiction medications, yet fully aware of the major disincentives to the industry, grappled with the issue of providing extraordinary incentives to the pharmaceutical industry. Several ideas were discussed at length, including those that were presented at the workshop. These included, granting a patent-extension on some other product marketed by a pharmaceutical company that develops an approved anti-addiction medication; removing the potential for price controls; advance special purchase of an anti-addiction medication; and/or creating a prize or bounty to the first few companies that produce an approved anti-addiction medication. Although, the committee could not adequately envision the implementation of those extraordinary incentives and did not reach a consensus to make specific recommendations on those issues, a majority of the committee agreed that certain of the incentives regarded as extraordinary should be deliberated by policymakers. Thus, in the final chapter of the report, two of those issues, which had support from a majority of the committee members, are presented, not as recommendations, but as approaches for further consideration.

As the committee worked throughout the year on the issue of developing anti-addiction medications, it become obvious that such medications could have enormous benefit and positive impact not only on the lives of drug-dependent individuals but on many aspects of American society. The committee is aware of recent studies which note that every dollar spent on drug treatment is worth seven dollars spent on law-enforcement efforts, clearly demonstrating the cost-effectiveness of treatment. Yet, pharmacotherapy, as an effective and viable adjunct to other treatment modalities, has received far too little attention from the research community, the pharmaceutical industry, public health officials, and the federal government. The committee considered obstacles, large and small, that impede the development of anti-addiction medications. It is the hope of this committee that the issues discussed in this report and its recommendations well be carefully considered not only by the National Institute on Drug Abuse, but also by the Congress and the executive branch as policy options for treating drug addiction are examined and priorities are set.

Laurence E. Earley

Committee Chair