How Methadone is Regulated

Even though the effectiveness of methadone for treating opiate addiction has been well-established, its use has long been controversial, a fact reflected in its extensive regulation. First, the manufacturing, labeling, and dispensing of methadone are subject to the general requirements of the FDA for establishing the safety, effectiveness, and consistent quality that are applied to virtually all prescription drugs under the Federal Food, Drug, and Cosmetic Act. Second, because methadone is a legal narcotic drug, its production, distribution, and dispensing are subject to the requirements applied to schedule II controlled substances by the Drug Enforcement Administration (DEA) to prevent diversion and illicit use.

In the case of methadone, a unique third tier of special standards has been established by the Department of Health and Human Services (HHS) prescribing how and under what circumstances methadone may be used to treat opiate addiction. These standards are implemented by FDA regulations, jointly with the National Institute on Drug Abuse (NIDA) since 1980 and, since 1993, with the Substance Abuse and Mental Health Services Administration (SAMHSA.) The FDA regulations issued in 1972 were designed to create a special ''closed system'' of distribution and use of methadone for opiate addiction treatment, restricted to hospital pharmacies and to physicians registered with both FDA and DEA who were authorized to dispense the medication in a treatment program only. This three-tiered system of federal regulation has continued for over 20 years and has recently been extended to a methadone analog, levo-alpha-acetyl-methadol (LAAM). The basic assumptions of this system have not been reviewed comprehensively during this period.

Methadone treatment of opiate addiction is often restricted still further by many state governments, a fourth level of regulation, a matter beyond the scope of this report. To complicate the picture even further, a fifth tier of regulatory authority over methadone treatment programs is sometimes found at the county and municipal level.

Two federal statutes require the Secretary of Health and Human Services to issue standards of treatment for narcotic addiction. Section IV of Title I of the Comprehensive Drug Abuse Prevention and Control Act of 1970 directs the Secretary to "determine the appropriate methods of professional practice in the medical treatment of the narcotic addiction of various classes of narcotic addicts." In addition, Section 3 of the Narcotic Addict Treatment Act (NATA) of 1974 required practitioners who dispensed methadone for maintenance or detoxification treatment to register each year with the Drug Enforcement Administration (DEA), which is instructed to register such applicants judged as qualified "under standards established by the Secretary" of Health and Human Services (originally Health, Education, and Welfare) to provide treatment services. Registrants are also required to comply with DEA's physical security and record-keeping requirements and with HHS's standards for "the quantities of narcotic drugs which may be provided for unsupervised use," namely, take-home medication.

Scope of the Report

The charge to the committee was to study current DHHS standards for narcotic addiction treatment and the regulation of methadone treatment programs pursuant to those standards. In this context, the committee sought to evaluate the effects of federal regulations on the provision of methadone treatment services and to explore options for modifying the regulations to encourage optimal clinical practice. It also considered the effects of the regulations on the development of new anti-narcotic medications, albeit briefly, as another IOM committee was convened to address this topic at length. Finally, it assessed the impact of the regulations relative to other factors affecting the provision of treatment services, and examined alternatives to the existing regulations.

In connection with the latter undertaking—examining alternatives to the existing regulations—a key point emerged concerning standards. Although the Secretary of HHS must set standards for narcotic addiction treatment, the sole means of doing so, historically, has been by federal regulations. But the implementation of standards by regulations is not required by law, and other options might be viable. In the course of developing this report, therefore, we examined alternative or complementary ways to implement standards, such as clinical practice guidelines and formal quality assurance systems (discussed on page 12 of this summary).

Although the study was limited to federal regulation of methadone, the report summarizes state rules in five jurisdictions—New York, California, Massachusetts, Illinois, and Florida. Unfortunately, a comprehensive description of the authorities and agencies of the states that govern opiate agonists used for treatment of opiate addiction does not exist. The limits of the charge and available data restricted the committee's evaluation of state regulation.

Balancing the Benefits and Risks of Methadone

Having completed its investigations, the committee urges reassessment of the appropriate balance between the risks of methadone and its benefits so that communities can attain the full potential benefit of this means of treating opiate addiction and its associated problems of crime, disease, and disorder, without increasing the risks of diversion and misuse. Current policy, in the committee's view, puts too much emphasis on protecting society from methadone, and not enough on protecting society from the epidemics of addiction, violence, and infectious diseases that methadone can help reduce.

Why, if methadone is effective, is it regulated so highly and so differently from other drugs? Three factors appear to have determined methadone's uniqueness as a regulated drug. First, methadone (and now LAAM), are the only opiates authorized for treating opiate-dependent persons. Thus, providing methadone to patients on a regular basis creates a potential for diversion and abuse. Second, the revision of regulations has been inhibited by inertia. Although the 1972 regulations were modified in 1980, 1989, and 1993, there does not appear to have been any major public effort to reexamine the underlying assumptions or long-term consequences of the regulations until this committee review was requested. Finally, neither public nor professional attitudes, nor those of the addict community, have supported methadone treatment strongly, and in the absence of this support the existence of federal regulations has provided local communities and society at large with assurance that their concerns about methadone were being addressed. In sum, the current regulations are predicated on a belief that the societal risks of methadone outweigh the societal benefits to such an extent that extraordinary controls are necessary above and beyond those applicable to any other therapeutic drug in the United States.

In the committee's view, this belief underlying the current regulations is not valid in today's environment and the regulations should be modified accordingly. The belief has its roots in the experience of the late 1960s and early 1970s, when knowledge of methadone was not extensive and the social risks associated with heroin use seemed largely confined to the addicts themselves. Today, however, we know much more about the risks and potential misuse of methadone. Although the drug can be abused, it is rarely a primary drug of abuse. Further, there is no apparent evidence of organized crime involvement in the street market for the drug.

At the same time, the committee finds that the current regulations produce unintended results: addicts who cannot obtain a treatment program tailored to their individual circumstances, physicians who are unable to exercise professional judgment in treating individual patients, programs that are isolated from mainstream medical care (thus depriving patients of important ancillary services), and significant economic costs in assuring compliance with regulatory requirements, costs that are shared by programs, insurers, patients, and taxpayers.

The committee has concluded that correcting these faults and, in general, raising the standard of treatment entails authorizing greater clinical discretion in medical treatment and reducing the scope of government regulation. There is no compelling medical reason, in the committee's view, for regulating methadone differently from all other medications approved by FDA, including schedule II controlled substances.

Nevertheless, the committee is not recommending abolition of the methadone regulations. Although, as stated above, there is no compelling medical reason for treating methadone differently, the committee recognizes that the regulations provide a number of positive benefits. The regulations address both a potential threat and a public fear of diversion. They help maintain community support for methadone treatment programs. They encourage comprehensive care and provide guidance to state authorities, hospitals, and medical practitioners. Although some believe that these latter goals can be accomplished by clinical practice guidelines alone, the committee believes that such guidelines, although necessary to guide practice, are not by themselves enough to assure that patients are cared for in a safe and thoughtful manner. Nor are they sufficiently developed at this time. The committee concludes that a need exists to maintain certain enforceable requirements in order to prevent substandard or unethical practices that have socially undesirable consequences.

In thus concluding that the regulations should be retained—but modified to give greater weight to clinical judgment, as determined by clinical practice guidelines—the committee considered one further aspect of the regulations. The regulations have been criticized as being "process-oriented"—imposing an undue administrative burden, infringing on clinical authority, and lacking any relationship to patient outcomes, program performance, and the quality of services provided. Although an "outcomes" approach might be useful, the committee believes that the current treatment system lacks the institutional infrastructure, including data systems, to support such a far-reaching step, a subject we return to below. Therefore, the committee recommendations to modify the regulations are ones that can be acted upon now, on the basis of existing empirical data. These recommendations include a number of changes in terminology, which emphasize that methadone and now LAAM involve the use of opiate agonist pharmacotherapy to treat opiate addiction, not the more pejorative and less descriptive "narcotic addiction,'' and that it is the addiction, not the addict, that is being treated. (All uses of narcotic in this summary and report refer to legal or official uses of the term, which is an unavoidable source of confusion.)

Recommendations to Modify and Supplement the Regulations

The IOM committee developed the following general principles, according to which the regulations

• Should encourage that approved methadone programs make comprehensive care available to all opiate-addicted patients;
• Should emphasize the need for continuing clinical assessment of patients throughout treatment;
• Should provide clear instructions to programs regarding the procedures for the involuntary administrative withdrawal of medication, termination of treatment, or discharge of patients for whatever reason, and provide rights of due process to ensure safe and humane treatment;
• Should not arbitrarily restrict clinical practice;
• Should not promote withdrawal from methadone maintenance treatment without regard to the probability that the patient will return to opiate addiction;
• Should prohibit basing medication dose level on patient participation in or compliance with the treatment program.

In what follows, we describe some of the ways we applied these principles in recommending changes in the regulations (discussed in chapter 7).

Enforcement of the Regulations

The committee has drawn four conclusions about how the methadone regulations should be enforced (discussed in chapter 8):

First, the Drug Enforcement Administration should focus its attention on standards for the physical security and record-keeping associated with the safe handling, storage, and dispensing of opiate medications (e.g., methadone and LAAM), as they do with other scheduled II drugs, but should have no role controlling or limiting medical practice.

Second, in response to the time-consuming, costly, and overlapping inspections of methadone treatment programs by federal, state, and, sometimes, county and municipal authorities, the committee recommends that the FDA, with SAMHSA and NIDA, conduct an extensive review of the methadone enforcement policies, procedures, and practices of all health agencies of government—federal, state, and local—for the purpose of designing a single inspection format that would provide the basis for single, comprehensive inspections conducted by one agency that would serve all agencies and that would improve the efficiency of methadone service provision by reducing the number of inspections and consolidating their purposes.

Third, to improve the competence of inspectors of methadone treatment programs, the committee recommends that FDA, SAMHSA, and NIDA develop an annual training program for inspectors, whether from FDA, DEA, or state and local government agencies; that such a training program review all aspects of methadone treatment so that inspections are better focused and informed; and that this program be designed to support the consolidated review recommended above.

Finally, the committee believes that is necessary for an effective enforcement effort to close seriously deficient programs. The committee does not subscribe to the proposition that any program is better than none. An effective compliance program should close or bring into compliance substandard programs.

Guidelines and Quality Assurance

As stated above, the committee has concluded that the scope of federal regulation of methadone treatment should be reduced in favor of authorizing greater clinical discretion in determining appropriate medical treatment (see chapter 8). One means of assuring that clinical discretion is exercised in a sound manner is through clinical practice guidelines, defined by a 1990 IOM report (Clinical Practice Guidelines) as ''systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances." Such guidelines are making their appearance in the substance abuse area, most notably in the Treatment Improvement Protocol (TIP) series of the Center for Substance Abuse Treatment (CSAT) of SAMHSA, and the committee considered them as a complete alternative to regulations. The committee concluded, however, that at this early stage of their development, guidelines are best employed as a complement, rather than a complete alternative, to existing regulations.

Formal quality assurance (QA) systems, either governmental or private, are another way to supplement reduced-scope regulations and shift responsibility for the provision of treatment services from regulators to clinicians. In the substance abuse area, formal QA systems are less well-developed than are practice guidelines. Designing a formal QA system involves selecting the outcome measures; devising instruments for measuring outcomes and for adjusting for severity of addiction and illness; and developing complex, valid data systems. The way substance abuse treatment is currently financed, no single revenue stream offers enough incentive to service providers to generate the requisite data. The Methadone Treatment Quality Assurance System, sponsored by NIDA, designed to assess the feasibility of a performance-based reporting and feedback system for methadone treatment programs, offers the prospect of laying the foundation for a formal QA system in the future.

Process Evaluation and Outcome Evaluation

Steps can be taken now, however, to set the stage for practice guidelines or QA systems (see chapter 8). In this connection, it needs to be pointed out that assessing quality requires process evaluation as well as outcome evaluation, and a way to relate the two. Process evaluation measures patient treatment procedures, which can be defined independently of the outcomes of care. For example, we suggest in the report that methadone maintenance patients be evaluated comprehensively for their medical, drug and alcohol, psychosocial, criminal, and employment problems; offered medical screening for AIDS, sexually transmitted diseases, tuberculosis, and hepatitis; given onsite counseling by well-trained and competently supervised professionals; and provided medical, mental health, and other social services, either on-site or by referral. These four processes could form the basis for QA process criteria standardized for clinical or administrative use by clinics or external evaluators.

While helping to assess whether therapeutic procedures are done "correctly" or not, however, process criteria do not indicate the effectiveness of the procedures. Effectiveness must be defined not only in relation to the individual well-being of the patient but also the public health and public safety objectives for methadone maintenance treatment, namely, the elimination of illicit opiate use and reduction of non-opiate illicit drug use; the general increase in positive social behaviors and employment; and the reduction of AIDS-transmission behaviors, crime, social violence, and the disproportionate use of medical and social services. We believe that the achievement of these objectives can and should be measured in any outcomes evaluation. Not every treatment program can by itself be expected to accomplish the full range of these objectives; achieving this goal will require integration and coordination with treatment services that may be provided by other agencies.

Outcomes can be objectively measured by medical and psychiatric examinations, evaluation of alcohol and drug use, verification of employment, and arrest records. Retention in treatment is a useful proxy measure of positive outcomes. The committee does not recommend that regulations be the vehicle for outcomes assessment; it urges instead that further steps toward instituting clinical practice guidelines and QA systems be taken.

Federal Government Leadership

The need exists, in the judgment of the committee, for stronger federal government leadership in four areas: research, federal-state relations, the financing of substance abuse treatment, especially as it pertains to the use of methadone, and guidance on substance abuse treatment policy within the DHHS (see chapter 8).

There are two research issues on which the committee wishes to comment. First, it concurs in the conclusion of an IOM committee examining the NIDA Medications Development Program that the dual regulation by both FDA and DEA of clinical research in controlled substances is an unnecessary impediment to the conduct of such research (IOM, 1995). It endorses the recommendation of the other committee that "action be taken to remove the adverse effects of DEA requirements, under the Controlled Substances Act (CSA), on clinical research involving controlled substances, by holders of active FDA Investigational New Drugs (INDs), either by amending the CSA to exempt such IND investigations from applicable DEA regulations or by the alternative administrative and regulatory measures."

Second, the ADAMHA Reorganization Act of 1992 required that 15 percent of the research funds of the National Institute of Mental Health, the National Institute on Alcoholism and Alcohol Abuse, and the National Institute on Drug Abuse be spent in health services research. In the case of NIDA, compliance with this requirement will undoubtedly involve research on the delivery of substance abuse treatment services, some of which may involve methadone, LAAM, or other controlled substances. This research may involve such issues as treatment settings and take-home privileges.

Such health services research must be permitted to experiment with various institutional arrangements and not be subjected a priori to regulations that force it into a pattern prescribed by the methadone regulations. That is to say, if drug delivery in such research must comply with existing methadone regulations, we will never learn whether there are safer and more effective ways to treat addiction using alternative means of drug delivery, or whether these alternative means affect the potential for drug diversion and abuse. The committee recommends that NIDA, in conjunction with SAMHSA, and FDA develop a general policy to guide health services research involving controlled substances such as methadone and LAAM, and negotiate a memorandum of understanding with the DEA to govern such research.

With respect to federal-state relations, the committee notes that although federal regulations establish a common framework for methadone treatment services, there is great variation among the states regarding methadone treatment services. This variation stems from philosophical and financial factors that appear unrelated to the prevalence of opiate addiction and the characteristics of the treated patient population. (The report, in chapter 6, summarizes state rules in five states—New York, California, Massachusetts, Illinois, and Florida.)

In the course of examining the federal methadone regulations, the committee arrived at several general conclusions about the responsibilities of the federal government and the states.

First, a need exists to maintain a federal system of regulations that proscribe certain activities, such as using medication doses to reward or punish a patient's behavior, or failing to provide due process for involuntary administrative termination of treatment. In addition, clinical practice guidelines should be developed for methadone treatment, with state substance abuse authorities as a primary user.

Second, the federal government should actively attempt to minimize the administrative burden associated with both federal and state government regulation of methadone treatment. It should seek compatibility of federal and state regulations, and should adopt uniform procedures that allow inspections by one level of government to be satisfactory for other levels. It should, as appropriate, consider the delegation of the inspection and compliance function to the states on a contract basis.

Third, federal regulations should encourage states, through their licensing boards, to ensure that medical, psychiatric, nursing, psychology, social work, and pharmacy staff have adequate training to provide the appropriate care in methadone treatment programs.

Fourth, federal regulations should prohibit states that receive federal funding from developing regulations or contractual requirements that arbitrarily limit services and deny methadone pharmacotherapy to patients who require concurrent treatment for psychiatric illness and/or other addictions, or from arbitrarily limiting services even in the absence of such regulations or requirements. SAMHSA should be authorized and directed to tie compliance with this requirement to eligibility for block grant funding.

Finally, the extent of state regulation of substance abuse treatment revealed in the case of LAAM, approved by FDA in 1993 for treating narcotic addiction, but not yet approved by many states is so great that the committee recommends that a comprehensive assessment of state substance abuse treatment regulations be undertaken, especially as they pertain to the treatment of opiate addiction, with an eye to developing a model state approach to the financing, treatment, and regulation of services.

With respect to financing, the committee was not asked to examine this aspect of methadone treatment, and the descriptive data in chapter 6 do not permit any authoritative judgments to be made about the adequacy of financing. Recent evidence indicates, however, that there has been a marked decrease in the number and variety of services clients reported receiving. Although there are currently federal block grant monies to improve access to treatment, they do not appear to meet the current treatment demand. These and other financing limitations create serious barriers to treatment for many patients and limit the type and quantity of provided services.

The committee notes two developments pertaining to treatment financing. First, the fiscal year 1995 budget submission sent to Congress by President Clinton in early 1994 requested increased funding for drug treatment services relative to law enforcement activities. Second, the omnibus crime bill adopted by Congress in 1994 emphasizes prevention and treatment of substance abuse. It may be expected that increased federal funds will flow to substance abuse treatment services as a result of these actions. Therefore, the committee recommends that DHHS conduct a review of its priorities in substance abuse treatment, including methadone treatment, in a way that integrates changes in regulations and the development of practice guidelines with decisions about treatment financing.

With respect to drug abuse policy within the DHHS, current organization as revealed in the area of methadone, results in department policy emerging from the independent activities of the several pertinent Public Health Service agencies—SAMHSA, NIDA, and FDA—and from coordination between these agencies. The committee concludes that federal policy on methadone treatment, and in all likelihood broader areas of drug abuse treatment, would benefit from sustained department-level policy oversight, informed by a clinical perspective, on all issues related to regulations, practice guidelines, and treatment financing.

The committee does not believe that such a policy oversight role requires a major organizational change within DHHS, but that one official in the Office of the Assistant Secretary for Health should be designated to serve this function for the department. The committee recommends that the Secretary of HHS direct the Assistant Secretary for Health to designate a senior official in the Office of the Assistant Secretary for Health to be responsible for policy oversight and guidance on methadone treatment and on related drug abuse prevention and treatment issues.

Reference

• Institute of Medicine. 1995. Development of Medications for the Treatment of Opiate and Cocaine Addictions; Issues for the Government and Cocaine Addictions; Issues for the Government and Private Sector, CE Fulco, editor; , CT Liverman, editor; , and LE Earley, editor. , eds., National Academy Press, Washington, D.C. [PubMed: 25121209]