State Of The Scientific Knowledge On Addiction

The initiating event leading to drug addiction is the administration of an agent, such as heroin or cocaine, to obtain a pleasurable effect. Addiction is characterized as the compulsive use of a drug despite adverse consequences. Key problems in addiction are how to prevent the onset of compulsive drug use and how to prevent relapse and the craving that leads to relapse (Chapter 2). In the past, much medical attention has been given to treatment (detoxification) for the symptoms of acute abstinence. Yet, knowledge about the pathophysiology of the syndromes of protracted abstinence and conditioned withdrawal or relapse is still rudimentary and presents an important challenge to development of anti-addiction medications.

Since the 1960s, it has become clear that the effects of opiate drugs are mediated through interaction with opioid receptors and interference with actions at those receptors presents a rational strategy for developing medications for opiate addiction. The mechanism of cocaine addiction is not well characterized, however, it is understood that the major pharmacological effect of cocaine is on the dopaminergic system of the brain. Unfortunately, the potential involvement of a wide range of neurotransmitter systems in cocaine's actions makes the development of a treatment medication difficult because no single target site is immediately apparent. In fact, an optimal strategy might require the use of several drugs that have different mechanisms of action.

In response to the absence of a well-defined mechanism of action or a compound for the treatment of cocaine addiction, MDD has developed the Cocaine Treatment Discovery Program (CTDP) to screen candidate compounds through a tiered strategy that uses both in vitro biochemical assays and in vivo behavioral tests. However, several factors limit the effectiveness of the screening protocols and their predictive value in humans, including the lack of knowledge of the mechanism of cocaine addiction; the lack of animal models for addiction, craving, and relapse; and the small number of compounds supplied to NIDA for screening. In its report, the committee makes several specific recommendations to MDD regarding the CTDP program.

Because the state of scientific knowledge of addiction is rudimentary, the committee believes that it is imperative to foster NIDA's basic-research efforts in the mechanism of cocaine addiction and in the molecular, cellular, and behavioral bases of chronic drug effects and the genetics of vulnerability to addiction. There is also a need for basic research to develop laboratory models of behavioral characteristics of the addictive process. The committee strongly believes that unless basic research is supported at an appropriate funding level, it will be difficult to make the necessary progress in the scientific knowledge base. The lack of such knowledge would continue to hamper the private sector and MDD in the development of a medication.

In relation specifically to MDD, the committee recommends two mechanisms to address the critical issue of supporting basic science:

The committee recommends that MDD be given a high priority for funding. Although MDD was authorized at $95 million in FY 1994, its appropriation of $40 million was considerably short of its authorization and is far below what is needed for research and development.

The committee is aware, however, of the budget constraints on the institutes of the National Institutes of Health (NIH); as a possible mechanism for increased support, the committee suggests the use of funds from the Special Forfeiture Fund in the Office of National Drug Control Policy (ONDCP).² Utilizing a portion of those funds for basic research not only would provide additional money to MDD, but would demonstrate executive-branch support.

The committee recommends that NIDA designate national drug abuse research centers, subject to congressional appropriations, as described in the ADAMHA Reorganization Act [P.L. 102-321, Section 464N (a)], ''for the purpose of interdisciplinary research relating to drug abuse and other biomedical, behavioral, and social issues related to drug abuse." Those centers would be engaged in and would coordinate all aspects of drug-abuse research, treatment, and education.

The paucity of basic knowledge is best approached through a coordinated effort, and the committee intends that such centers serve as focal points for all aspects of drug-abuse research and their designation would have the added benefit of encouraging new investigators to enter the field; the centers would also serve as sites for clinical trials and for training clinicians. With the designation of such centers, the committee believes, progress will be made in basic and clinical research on the treatment of drug addiction (Chapter 2).

Nida's Medications Development Division

In recognition of the need to stimulate the availability of medications to treat drug addiction, the Anti-Drug Abuse Act of 1988 (P.L. 100-690) authorized funds for a drug discovery and development program in NIDA. Beginning with an appropriation of $8 million in 1988, NIDA launched a Medications Development Program in its Division of Preclinical Research. Building on this program, NIDA formally established the Medications Development Division in 1990. The primary strategy adopted by MDD is to work with industry to perform the research and development necessary to secure FDA marketing approval for new medications to treat drug addiction. MDD does not operate inhouse laboratories or clinical-development programs to fulfill its mission. It manages this work through multiple external instruments, such as contracts, grants, and interagency and collaborative agreements (Chapter 3).

While the current budget of $40 million and staff of 33 full-time equivalents (FTEs) might be adequate to support the development of a small portfolio of products based on drugs that are already in use, the committee believes that they are insufficient to support basic research. Additionally, MDD has had difficulty in stimulating private-sector interest, in acquiring industry partners, and in obtaining a suitable number of compounds for screening. MDD had originally developed a screening agreement in which a compound's structure is made public after a 3-year period of confidentiality. That agreement has hindered MDD's ability to acquire compounds and affected MDD's capability to develop its screening program adequately because many companies did not want their confidential data to be made public. Thus, in 1994 MDD revised their original screening agreement and now all screening data from industry compounds will remain confidential. That change in policy should have a beneficial effect on MDD's screening program.

Although the committee commends MDD for the establishment of anti-cocaine and anti-opiate screening programs, the lack of established in vitro screening methods and validated animal models that are predictive in humans, especially for anti-cocaine medications, limits the utility of the screening program. The committee feels that there is a need for basic research to develop laboratory models of critical behavioral characteristics of the addictive process.

Improvement of such methods and models should be given a high priority for grant and contract support by MDD.

It became apparent to the committee, during its review of MDD and numerous meetings with industry representatives, that strong leadership is needed in promoting pharmacotherapy as an important component of our national strategy. Leadership must come from many sources, especially from the highest levels of the federal bureaucracy. However, an important leadership role belongs uniquely to NIDA and especially to MDD. MDD must view itself as the leader in stimulating private-sector interest in developing anti-addiction medications. The committee views this national leadership role as one of the key functions of MDD. Consequently, it should be empowered to lead, as well as to fulfill, a scientific and technical mission.

The committee recommends that NIDA and MDD, in determining how to improve MDD's relationship with industry, evaluate the applicability of the techniques already in use by the Developmental Therapeutics Program of the National Cancer Institute, the National Cooperative Drug Discovery Groups on Acquired Immune Deficiency Syndrome of the National Institute of Allergy and Infectious Disease, and the Anticonvulsant Drug Development Program of the National Institute of Neurological Disorders and Stroke.

Those are all programs (Appendix E) of similar mission within NIH that have established effective working relationships among leading academic and government scientists, FDA, and individual drug companies through a combination of scientific communication, mutual technical assistance, cooperative agreements, and licenses. In the committee's view, the primary policy responsibility of MDD should be to provide such leadership as a complement to its scientific responsibilities (Chapter 3).

Effectiveness Of Treatment

There is strong consensus that methadone maintenance treatment is effective for the treatment of opiate addiction (IOM, 1990; OTA, 1990; Anglin and Hser, 1992; Prendergast et al., in press). Treatment is effective in reducing opiate use, criminal activity, and intravenous drug use. The evidence of treatment effectiveness is not as strong for cocaine treatment, yet there is an accumulating body of research pointing to the effectiveness of psychosocial treatment modalities. As yet, there is not a pharmacologic agent for the treatment of cocaine addiction or a medication to reduce cocaine craving.

Treatments for opiate and cocaine addiction are cost-effective (Chapter 4). When the cost of opiate and cocaine treatment is compared to the benefits in reduced crime, the result is unambiguous: every dollar invested in treatment yields at least two and up to four dollars, and sometimes more, in societal benefits (Gerstein et al., 1994). Treatment also averts other health care costs. In short, current treatments for opiate and cocaine addiction, while variable in nature and cost, are both effective and cost-effective. Clearly the federal government should make every effort to expand the treatment capabilities of the states. New medications, especially for cocaine addiction, do hold the potential to reduce some of the need for counseling, which forms the largest share of treatment charges. With lower overall treatment costs, treatment can prove to become even more cost-effective.

The committee strongly recommends expanding the treatment capabilities of the states for opiate-and cocaine-dependent individuals to ensure that all those seeking treatment obtain it without delay. The recommendation may be implemented by:

• Providing additional money to increase treatment in states where there are waiting lists.
• Shifting money from supply control programs to treatment programs.

Treatment Financing

The financing³ of treatment is often cited by the pharmaceutical industry as yet another deterrent to the development of anti-addiction medications (Chapter 5). Prominent reasons are the fact that so few patients have private insurance and there is a concomitant need to rely on direct public subsidy to pay for their treatment (IOM Workshop, June 13, 1994).

The annual payments for methadone maintenance treatment are estimated at $480 million in FY 1993. There are an estimated 117,000 patients for whom annual expenditures are about $4,100 each. Currently the financing of methadone treatment is deeply dependent on the public sector, primarily in the form of federal block grants and state alcohol and drug agency funds. Despite the sizeable public role in financing, neither state agencies or the federal government have consolidated their potential market leverage to secure discounts on large volume pharmaceutical purchases. Private insurance payment is almost insignificant. Patients are willing to pay their share, but were treatment to become more costly, patients are not likely to have the resources to absorb increased costs.

State financing has been and is expected to be a major impediment to the sale of LAAM, according to both BioDevelopment and clinic operators. State financing practices can be so rigid that they effectively block the introduction and adoption of a new medication. The flow of funds to clinics is dictated by the policies and regulations of two separate state agencies: the state alcohol and drug agency, which administers state funds and federal block grants, and the state Medicaid agency, which administers state and federal Medicaid dollars. There is widespread variation in funding practices (IOM, 1995), but either state agency can erect financial barriers to the adoption of a new medication. New York set a flat daily or weekly fee per patient (which usually includes all services without specifying the amount for medication and dispensing), and other states have set a flat fee for a "dosing visit," the dispensing of one dose of medication. California, authorizes ceilings on the number of publicly funded patients that can be treated at each clinic (Goldstein, 1989). Under these funding practices, LAAM is at a disadvantage because it is more expensive than methadone, the medication for which reimbursement rates have been structured over the past 20 years. To obtain better reimbursement, clinics must petition the appropriate agency for more favorable rates.

Financing and regulatory obstacles are contributing to the stalled market penetration of LAAM. LAAM's higher price may have exacerbated the problem, but the rigidity of the financing and regulatory structure antedates its introduction. This is unfortunate as LAAM is potentially more effective therapeutically. Even one of LAAM's selling points for public health—the prospect of increasing clinic patient loads—has become a disincentive for state alcohol and drug authorities struggling to find additional funding not just for LAAM, but for the higher costs of counseling and comprehensive treatment for possibly more patients. If BioDevelopment Corporation succeeds in securing adequate financing, that will serve as an incentive to other pharmaceutical companies. If not, the future for other opiate medications does not appear encouraging. Therefore, the committee strongly urges state and federal agencies to work together, not only to provide an incentive to pharmaceutical companies, but in the interest of public health, to facilitate the availability of newly approved anti-addiction medications. Possible mechanisms that the states and federal government might consider include requiring all Substance Abuse Block Grant recipients to offer those medications to patients and assuring appropriate financing of new medications by state alcohol and drug agencies and their counterpart Medicaid agencies. Those actions would have the additional benefit of providing a strong signal to pharmaceutical companies demonstrating state and federal commitment to the development of anti-addiction medications (Chapter 5).

Training And Education

Although the limited availability of scientists and clinicians specializing in drug abuse research and treatment has direct consequences for the delivery of health care services and research on new treatments, it has a less obvious, but equally important, effect on pharmaceutical R&D investment. Pharmaceutical companies traditionally market their products to health care professionals and promote their products through personal visits by sales representatives, through journal and mail advertising, and through support of scientific symposia and continuing medical education. Pharmaceutical companies distribute their products through hospital and community pharmacies, pharmacy chains, and distributors. To the extent that the treatment of drug dependence is often delivered outside that system by specialized clinics (e.g., narcotic treatment programs, typically with part-time physicians and limited marketing opportunities for pharmaceutical companies), and to the extent that drug abuse treatment involves many fields of medicine (e.g., family practice, internal medicine, psychiatry), pharmaceutical companies see greater difficulty in marketing anti-addiction medications than in marketing other products. Pharmaceutical firms also rely on academic clinical investigators and practicing clinicians to advise them on drug development issues such as current therapeutic trends, the role of drugs in the overall treatment strategy, unmet medical needs, indications to be evaluated, clinical trial design, and appropriate therapeutic endpoints.

The committee believes that a long-term national effort is needed to strengthen the substance abuse education and training of both specialists and primary care physicians. That effort will strengthen the infrastructure needed for research and treatment and will encourage pharmaceutical investment in this field (Chapter 6).

The committee recommends that the federal government increase its efforts to attract researchers and clinicians to the field of drug addiction treatment. That may be accomplished by implementing one or all of the following options:

• NIDA's training budget could be increased, but not at the expense of their research programs. Requests from NIDA for large increases in its training budget have not been filled in FY 1993 or FY 1994, and NIDA has received a lower percentage of training funds than several other institutes. Increasing NIDA's training budget such that it will enable NIDA to offer fellowships that are competitive with private sector salaries, and therefore, more attractive to potential candidates would "jump-start" the expansion of the field of drug addiction treatment and research; it could have nationwide impact by increasing the numbers of scientists and physicians recruited, trained, and working in the field of drug addiction.
• An educational loan repayment program in return for work in drug abuse-related clinical research could attract young physicians with substantial educational debt into careers as clinical investigators.
• Mid-career programs could be developed to encourage a cadre of practicing physicians and scientists to enter the field of drug addiction treatment and research.

The committee recommends an increased emphasis on drug abuse education throughout medical school and primary care residency programs. To accomplish this, the following could be implemented:

• Drug abuse education could follow a systematic, integrated approach to coordinate the curriculum across specialty departments.
• Training institutions could develop affiliations with community-based treatment centers, where feasible, to provide student access to multiple treatment settings.
• The National Board of Medical Examiners ⁴ and the primary care specialty boards of the American Board of Medical Specialties (ABMS) could pay increased attention to drug abuse issues, skills, and knowledge on their examinations for certification.
• Faculty development programs could receive increased federal support. The Center for Substance Abuse Prevention's Faculty Development Program which trains medical school faculty members to serve as role models, educators, and mentors in the field of drug abuse research and treatment is a good model.

The committee recommends that comprehensive drug abuse centers be developed to engage in and coordinate all aspects of drug-abuse research, treatment, and education. Further, the committee recommends that NIDA and the Substance Abuse and Mental Health Services Administration (SAMHSA) work together to coordinate the effective and efficient use of existing centers by adding, where feasible, research, training, and/or treatment components.

Federal Regulatory Issues

State Regulatory Issues

State laws and regulations also affect the discovery, development, and marketing of anti-addiction medications, especially if the medication is a controlled substance (Chapter 8). Current medications to treat opiate addiction (methadone and LAAM) are schedule II narcotics that are tightly regulated, not only under the federal CSA and the Narcotic Addict Treatment Act (NATA) but under companion state laws. There are 51 sets of laws and regulations (for each state and the District of Columbia), that are counterparts to the comprehensive federal regulatory structure for controlled substances.

State and federal controlled substances acts are designed primarily to govern the possession, use, sale, distribution, and manufacture of medications that have a potential for abuse. Most state CSAs contain regulatory mechanisms, terminology, and provisions similar to those contained in the federal CSA; although, there are significant differences between federal provisions and states' provisions and variations in statutes from one state to another (NCJA, 1991). A failure to understand the regulatory framework in each state can lead to significant delays in clinical research development, marketing and use of a new anti-addiction medication, as shown by a case study of LAAM (Chapter 8). Any perceived delay in a return on investment to a pharmaceutical company can influence the decision to develop a new anti-addiction medication. Inasmuch as this area is already perceived as a marginal business investment, the additional overlay of the state regulations and the resulting delays can further deter companies from entering this field of medications development. That could be particularly true for smaller companies that have limited regulatory resources. Smaller companies may have an additional disadvantage if they have a limited number of products, and cannot afford the time lag before realizing a return on their investment.

A case study of the state regulatory hurdles faced in the market launch of LAAM, highlights some of the problems resulting from state regulations and demonstrates that state by state acceptance of LAAM, for marketing purposes, has been necessary even after final FDA approval of LAAM and rescheduling by DEA. The regulatory areas that pose the greatest problems for LAAM are scheduling and rescheduling procedures, amendment of treatment regulations, and the approval of treatment clinics. As illustrated by LAAM, regulatory regimes that were created with the intention of controlling abuse of illicit substances can prove unwieldy and counterproductive when they are applied to a therapeutic product. Of course, future anti-addiction medications might not be Schedule I or II narcotics—or even controlled substances—in which case many of the problems associated with LAAM would not occur.

While state inactivity is rescheduling can result in long delays in moving a drug from schedule I (under state Controlled Substances Acts) to schedules II to V, this situation is brought about in part by the current federal policy of interpreting ''currently accepted medical use in treatment in the United States" (for purposes of scheduling under the Controlled Substances Act) as requiring NDA approval. As a consequence of this policy is that the regulatory process at the federal level is prolonged for all newly approved drugs that are controlled substances (Chapter 7); this regulatory delay can become years when the rescheduling process requires both state and federal action and cannot begin until NDA approval, e.g., LAAM. The committee believes that the public health would be best served by an interpretation of the "currently accepted medical use" clause in the Controlled Substances Act that would recognize the use in humans under an IND and permit the scheduling process to begin at the time of NDA submission. The information required for scheduling a drug is already required to be in a self-contained section of the NDA. That section could be reviewed on a fast-track basis by FDA, and a scheduling recommendation could be sent to DEA well ahead of NDA approval. Scheduling could be done contingent upon final FDA approval. That approach would permit states to reschedule schedule I drugs closer in time to final FDA approval, minimizing delays such as the one now affecting LAAM, and have no negative drug control implications. Furthermore, it would remove a significant regulatory disincentive at the federal level that affects all scheduled drugs, not just schedule I substances. The committee concludes that if the current situation continues unchanged, it will have a chilling effect on private sector investment for any medication that may potentially meet the legal definition of a narcotic.

The committee recommends that the Office of National Drug Control Policy (ONDCP) direct DEA, in consultation with FDA and NIDA, to revise its policy on determining when a drug has a currently accepted medical use in treatment so that, for new therapeutic drugs that are also controlled substances, the process of scheduling can begin as soon as possible after submission of the NDA.

The committee believes that additional steps should be taken by federal agencies within the existing system to reduce future state obstacles. The committee proposes a two-step set of actions, interim and long-term. There are two interim steps federal agencies (ONDCP, FDA, SAMHSA, NIDA, and DEA) should take under existing authorities to ameliorate the delays, complexity, and lack of uniformity at the state level.

Market Obstacles And Creating Incentives

Need For Federal Leadership

The committee has considered and attempted to bring clarity to the multiple components involved in the development of anti-addiction medications. Such development depends critically on cooperation between the public and private sectors. Yet the number of federal agencies involved, current agency funding and staffing levels, regulatory requirements, remaining scientific questions, and other issues present difficult challenges to successful partnership and cooperation. Although many of the challenges are addressed in this report, it is important to recognize that government policies have not provided a strong emphasis on pharmacotherapy for the treatment of drug addiction. This lack of federal leadership represents an additional disincentive to industry, in that it affects the public sector's ability to establish clear guidelines, enhance interagency cooperation, and provide research programs with the stability necessary for medication discovery and development (Chapter 9). In addition to its role in developing medications for drug addiction, the government is likely to be the major purchaser of those medications. Thus, government policies are critical in determining the environment in which such medications are developed and are necessary for supporting pharmacotherapy as an important and accepted form of treatment.

The committee applauds the current emphasis on treatment in the 1994 National Drug Control Strategy and suggests an additional action to underscore the importance of treatment and strengthen federal leadership.

One option might be for the President to issue an executive order assigning a high priority to the development of medications for drug-abuse treatment. This, or some other explicit action, would enhance cooperation among the government agencies involved, focus their activities, and aid in the removal of existing institutional barriers.

Explicit action at the Presidential or cabinet level would have the added benefit of signaling to the private sector that the development of anti-addiction medications is a matter of high national priority. The committee further believes that progress in this area should be monitored. Thus, any action taken should include a provision for reporting by the involved agencies regarding their efforts to coordinate with other agencies and remove barriers identified. Examples of specific ways in which cooperation could expedite development of anti-addiction medications are formalization of agreements between NIDA and the Department of Veterans Affairs for support of clinical trials, and encouragement of all agencies to promote cooperation with the private sector. Other strategies, including the use of executive-level task forces and commissions, may also be options to strengthen federal leadership and give the issue high priority in the eyes of both the public and private sectors.

Conclusions

In reviewing the obstacles presented to the pharmaceutical industry for the development of anti-addiction medications, it is clear that, the disincentives outweigh the incentives. The formidable scientific and marketing issues, regulatory complexities, and financial uncertainties add up to an unattractive picture to the pharmaceutical industry, which tends to enter R&D investment from a high risk-high reward perspective.

Although it is possible to envision incentives that would interest some pharmaceutical companies (e.g., small pharmaceutical companies, biotechnology companies, or those companies already involved in the development of CNS compounds) without strong federal leadership, in establishing the role of pharmacotherapy and a long-term federal commitment to research, the committee believes all other efforts are likely to falter. As the federal government considers policies that will remove obstacles, the committee suggests a tiered approach of incentives, allowing each tier of incentives time to produce the desired effect (Chapter 9). For example, the first action may be the removal of disincentives, then the creation of modest incentives, and finally the development of extraordinary incentives.

The removal of disincentives includes many of the committee's administrative recommendations: use of orphan drug and fast track mechanisms for anti-addiction compounds; removal of adverse effects on clinical research of DEA requirements under the Controlled Substances Act; and counting DEA review time as part of the regulatory process for purposes of patent term extension for controlled substances.

The creation of modest incentives should include broad interpretation of the Orphan Drug Act to include anti-addiction medications or similar legislation to stimulate the market in the development of anti-addiction medications; a strong federal leadership role in support of treatment of drug-dependent patients; funding of basic research and training; adequate funding of treatment; and a modification or elimination of the "reasonable pricing clause" in CRADAs.

Finally, the committee considered two extraordinary incentives that the executive branch and the Congress may wish to consider. They are presented below as options for consideration, and they are not committee recommendations.

Options For Further Consideration

The committee discussed whether the overall strategy (i.e., strong federal leadership regarding drug abuse treatment and support of research) coupled with removal of obstacles to anti-addiction medication R&D would be likely to result in activity by the pharmaceutical industry. Additionally, the committee considered whether a considerable economic incentive specifically intended to reward the development of new anti-addiction medications was needed. The committee did not reach a consensus on that issue and has no formal recommendation for such an extraordinary incentive.

Nevertheless, the committee wishes to include in this report a brief description of two incentives that were supported by a majority of its members, recognizing that the committee has not provided details for implementation of those incentives (Chapter 9). Both of the following proposals are limited to medications developed for cocaine addiction and are intended to create a guaranteed market in view of the limited potential for return on investment of anti-addiction medications as perceived by the pharmaceutical industry.

Option 1 would offer developers of the first few (e.g., two or three) FDA-approved medications for the treatment of cocaine addiction for 3 years after approval a federal subsidy of a maximum of $50 million for purchase of the drug. The subsidy could be given, for example, through reimbursement of the copayment portion of medications for patients with health insurance and the full cost of medications for those patients without medical insurance.

Option 2 would allow for standing federal purchase orders for prearranged quantities and at an adequate price of one or more new cocaine treatment medications to begin at the time of FDA approval. The purchase orders would establish unambiguous confirmation of a market demand for those products, thereby stimulating investment and commercialization.

The options presented above were favored by a majority of the committee. Most committee members also favored implementation of those extraordinary incentives only if the first two tiers of recommendations fail to stimulate progress in the anti-addiction medications market. A majority of the committee agreed, however, that the above options should be deliberated by the executive branch and Congress as they develop policies to stimulate this area of research and development (Chapter 9).

References

• Anglin MD, Hser Y. 1992. Treatment of drug abuse. In: Watson RW, editor. , ed. Drug Abuse Treatment. New York: Humana Press. Vol. 3 , Drug and Alcohol Abuse Reviews.
• Gerstein DR, Johnson RA, Harwood HJ, Fountain D, Suter N, Malloy K. 1994. Evaluating Recovery Services: The California Drug and Alcohol Treatment Assessment (CALDATA). Sacramento, CA: California Department of Alcohol and Drug Programs.
• Goldstein HM. 1989. The Availability of Methadone Maintenance in California. Drug Abuse Information and Monitoring Project (DAIMP) White Paper Series 9. Los Angeles: UCLA Drug Abuse Research Center, DAIMP. Prepared for the California Department of Alcohol and Drug Programs.
• Hunt DE, Rhodes W. 1992. Characteristics of Heavy Cocaine Users Including Polydrug Use, Criminal Activity, and Health Risks. Prepared for the Office of National Drug Control Policy by Abt Associates, Inc.
• IOM (Institute of Medicine). 1990. Treating Drug Problems. Gerstein DR, editor; , Harwood HJ, editor. , eds. Washington, DC: National Academy Press.
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• OTA (Office of Technology Assessment). 1990. The Effectiveness of Drug Abuse Treatment: Implications for Controlling AIDS/HIV Infection. Washington, DC: OTA. OTA-BP-H-73. AIDS Related Issues Background Paper 6.
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Footnotes

1

Drug addiction is defined as the compulsive use of a drug despite adverse consequences. This report focuses on opiate and cocaine addictions and does not address alcohol and nicotine addictions.

2

The ONDCP Special Forfeiture Fund results from the transfer of money from the Federal Asset Forfeiture Fund (described below). In FY 1990, the Federal Asset Forfeiture Fund transferred $117 million to federal law-enforcement agencies. Deposits of $17 million were also made to the Special Forfeiture Fund to supplement ONDCP program resources and of $115 million to support Federal prison construction. The use of the Special Forfeiture Fund is at the discretion of the director of ONDCP.

The Federal Asset Forfeiture Fund is a sum of money resulting from the sale of assets used in criminal activity that have been seized by the government. In 1990, DEA seized assets valued at more than $1 billion. About two-fifths of the assets seized by DEA was currency valued at almost $364 million. In addition, DEA seized $346 million worth of real property, 5,674 vehicles worth over $60 million, 187 vessels valued at over $16 million, and 51 airplanes worth over $25 million. Almost two-thirds of DEA's seizures during 1990 resulted from cocaine investigations. DEA seizures that were ultimately forfeited are valued at more than $427 million in 1990.

3

Financing is generally defined as the payment or reimbursement for the cost of treatment made by private insurance, Medicaid, the patients themselves, or other sources. Financing is important to pharmaceutical investment because it has a critical effect treatment supply and the demand of treatment (Rogowski, 1993).

4

The National Board of Medical Examiners prepares and administers to medical students a two-part examination that is accepted by individual states as part of licensing.

5

In the mid-1980s, FDA routinely issued NDA "approvable" letters for drugs proposed for scheduling. In 1986, FDA changed its policy regarding NDA approvals for drugs pending scheduling and issued final "approval" letters with the addition of a statement that the drug could not be marketed until it was scheduled by DEA. The result was that the "clock" measuring time before patent expiration, for DPC-PTR Act purposes, was started, even though the drug was not able to be marketed. Under current FDA policy, issuance of a final approval letter seems to permit sale under the Food, Drug and Cosmetic Act without restriction, and no provision of the Controlled Substances Act applies to a drug that is not controlled under that Act.

6

ONDCP as previously drafted and put forth model state legislation on numerous topics, thus there is a precedent for model legislation on research and development of anti-addiction medications.

7

Section 8.3 of the NIH Patent Policy Board's Model CRADA states, "NIH have a concern that there be a reasonable relationship between the pricing of a licensed product, the public investment in that product, and the health and safety needs of the public. Accordingly, exclusive commercialization licenses granted for NIH intellectual property rights may require that this relationship be supported by reasonable evidence."