Treatment, Financing, and Costs
The development of pharmacotherapies for drug addiction treatment provides an opportunity to substantially expand and improve the treatment of addiction. However, for these treatments to be successful, they must be integrated both into specialty addiction treatment programs and primary care medical practices. Historically, the development of distinct organizational and financial structures for treating drug and alcohol problems separately from other medical disorders has generated obstacles to this integration (Thomas and McCarty, this volume). The committee believes that new pharmacotherapies will only be effective to the extent that clinicians accept them in either specialty or primary care settings and their use is facilitated through adequate financing, organizational structures, and community support.
While the historical pattern in the United States has been of relatively rapid adoption of new pharmacotherapies, the adoption of medications to treat drug and alcohol dependence has been quite limited (Thomas and McCarty, this volume). No medication has been used by more than 25 percent of the affected population, and some have been used by less than 5 percent. The underuse of medications for addiction treatment has many root causes: societal ambivalence about whether addiction is a moral failure or a medical disorder (Lowinson et al., 1992); the general perception that medications for addiction treatment either do not work or represent substitution of one addiction for another (Woody and McNicholas, this volume); the weak efficacy or lack of patient acceptability of some medications (Krystal et al., 2001); and the perception that addiction is an acute, rather than a chronic, relapsing disorder that requires extended treatment
aimed at preventing relapse and reducing the severity of complications (McLellan et al., 2000). Underdosing of individuals with currently available medications has also been a problem (D’Aunno and Pollack, 2002).
These perceptions and attitudes are reflected in the separation between addiction treatment programs and regular medical care, a separation that perpetuates multiple barriers to the use of medication treatment for addictions. The clinical challenge of creating treatment programs tailored to the unique needs of the individual patient, as well as to the specific drugs to which he or she is addicted, is made more complicated by the existence of separate medical and addiction treatment systems. Moreover, the use of immunotherapies and sustained-release formulations will require complementary interventions with behavioral therapies, representing a major challenge to current practitioner and provider structures.
This chapter first reviews potential barriers to the integration of immunotherapies and sustained-release formulations in specialty addiction treatment programs and primary care medical settings. In the specialty setting, medical expertise and infrastructure must be developed or coordinated with behavioral interventions; in the primary care setting, behavioral interventions must be made available or developed for coordinated delivery with the medication treatments. The chapter then reviews the currently available medications for treating substance abuse disorders, identifying some lessons learned by the adoption of (or failure to adopt) these medications in substance abuse treatment. Lastly, we briefly consider some cost and related economic issues.
SPECIALTY ADDICTION TREATMENT SETTINGS
Current specialty addiction treatment programs do not routinely provide extensive medical services, and when medical services are provided, they are ancillary to the central role of psychosocial behavioral treatment (Substance Abuse and Mental Health Services Administration, 2002). The absence of medical services reflects organizational structures and staffing patterns in addiction treatment programs (D’Aunno, Vaughn, and McElroy, 1999; Nohria and Gulati, 1995), the philosophical resistance of staff to using medications for addictive disorders (Woody, 2003), and financing limitations that arise from the way that specialty addiction treatment is provided (Coffey et al., 2001; Mark et al., 2000).
Most specialty addiction care is provided in small, outpatient clinics that have little overlap with the larger general medical system, and they
have organizational structures, staffing patterns and other resources that are neither physician centered nor involve physician delivery or oversight (Substance Abuse and Mental Health Services Administration, 2002). Even the opioid treatment programs that use methadone or levo-alpha acetyl methadol (LAAM) generally have minimal medical oversight, and most lack even rudimentary medical diagnostic or primary care delivery capability (D’Aunno et al., 1999). The absence of medical staff poses a barrier to the adoption of new medications in specialty addiction treatment settings.
In order to provide immunotherapies and sustained-release formulations in specialty addiction treatment settings, substantial additional resources would be required to integrate medical services and medical personnel in these settings. Moreover, immunotherapies, particularly monoclonal antibodies, will need to be administered in a medical setting where emergency medical treatment is available.
Specialty treatment settings may also be limited in their ability or interest in adopting new pharmacotherapies due to philosophical resistance. Most addiction treatment staff have been trained in one or more psychosocial treatment approaches (e.g., 12 steps; cognitive behavioral therapy, relapse prevention). They understand these approaches, know they work with many patients, and have little motivation to use medication. Lack of training and understanding of the effects and side effects of addiction medications, and discomfort with the research supporting the use of medications, are additional barriers (Mark et al., 2000; Owen, 2002; Thomas, 2000; Thomas et al., 2003). Although the potential value of medications may be acknowledged, there may also be deep skepticism.
This philosophical difference emerges partly from a particular interpretation of the 12-step approach of Alcoholics Anonymous (AA). Although AA founder, Bill Wilson (1955), emphasized collaboration between 12-step programs and the medical profession, many 12-step programs developed a drug-free philosophy that extended even to psychoactive medications for major depression or other serious, nonsubstance related mental disorders, and many patients were pressured to stop all medications (Woody and McNicholas, this volume). The strong personal experiences of staff with recovery without the use of medications may have promoted opposition to the use of medication even when combined with psychosocial treatment. These antimedication biases have diminished, especially concerning patients with dual addiction and mental health diagnoses, but they are often still strong in the case of antiaddictive medications.
The financing and structure of specialty services for addiction treatment have developed idiosyncratically and relatively autonomously from the nation’s system for medical care (Coffey et al., 2001; Mark et al., 2000). This isolation also poses a barrier to the integration of new immunotherapies. The presence of a large and autonomous system of specialty dependency treatment for chemical addictions reflects a legacy of poor service for alcohol and drug use disorders in health care and mental health care settings, limited coverage in health plans, and the resulting divergence in payer sources and regulatory mechanisms.
These financing problems have been further exacerbated by efforts to reduce health care costs. Medication costs seem high because their use requires medical personnel, who are the most expensive staff that can be hired in substance abuse treatment programs (Woody and McNicholas, this volume). Poor reimbursement for addiction treatment discourages treatment programs from adding these services, and medical personnel can usually earn more in other work (Thomas and McCarty, this volume). Addiction treatment often is disproportionately affected by cost-cutting efforts, and medical and other more highly paid staff become prime targets for elimination.
The availability of immunotherapies and sustained-release formulations will raise a host of questions for specialty addiction treatment settings. Research will need to explore the most effective clinical models for integrating medical services with psychosocial and behavioral treatment in specialty addiction settings. How medical personnel can be made available to administer medications and the effect of those personnel on nonmedical addiction treatment providers will need to be determined. In addition, models of public and private insurance that cover both medical and psychosocial treatment services will need to be developed and evaluated. At all levels, research should explore barriers to the use of immunotherapies and sustained-release formulations in specialty addiction treatment settings.
PRIMARY CARE SETTINGS
Medical settings offer the possibility of engaging patients with substance abuse diagnoses earlier in the course of their addictions and providing services to those who cannot or will not seek specialty care (Stein and Friedman, 2001; O’Connor and Samet, 2002). Despite these potential benefits, primary care settings have yet to routinely provide substance abuse treatment. There are a number of organizational, financing, and privacy-related considerations that have hindered such treatment
(Thomas and McCarty, this volume). These factors need to be taken into consideration as immunotherapies and sustained-release formulations are used for patients in medical settings.
Primary medical care settings are typically organized around procedural services and medications as the focus of treatment. While a portion of primary care has always been devoted to management of conditions that require ongoing psychosocial therapy, the linkages with psychosocial support systems have been largely secondary to medical therapy. Primary care providers often lack specific training or skills for substance abuse screening or treatment, have limited time to address problems of substance abuse, and have limited referral resources for specialized addiction counseling (Ferguson, Ries, and Russo, 2003; O’Toole et al., 2002; Friedmann, Alexander, and D’Aunno, 1999). The stigma associated with addiction problems also impedes efforts to provide appropriate services (Weissman, 2001).
Problems of addiction and its treatment share many features of other chronic medical disorders, such as diabetes or heart disease, which also require combined medication and behavioral treatment. To the extent that medical practices can incorporate chronic disease management strategies—including patient education, behavioral counseling for adherence and life-style change, and collaboration between physicians and other health care providers (nurses, pharmacists, counselors)—they will be successful in providing immunotherapies and sustained-release formulations for addiction treatment.
Differences in financing between general medical care and mental health and substance abuse treatment also will challenge the adoption of new therapies. The lack of insurance coverage parity between medical and addiction treatment complicates their integration, as many medical insurance programs limit funding for counseling and recovery support. Insurance benefits often require separate providers for medical and addiction services and deny reimbursement to medical providers who bill for addiction services. The financial incentives for delivery of screening and treatment for addictions in primary care are very limited, partly because there are no standard billing codes for reimbursement of these services. When providers are paid a monthly fee for all services (capitation), there is an incentive to limit new or expensive medications unless they save provider groups money in the short term.
A special challenge for the promotion of linkages between primary care medical and specialty addiction services is the complexity of communicating across settings in the context of federal confidentiality regulations for drug and alcohol treatment records. Medical practices that want to provide these treatments need to comply not only with the Health Insurance Portability and Protection Act (HIPPA), but also the more stringent requirements of 42 CFR, which requires that addiction treatment records be segregated for the purposes of disclosure to various entities. These requirements present a greater barrier for primary care providers, who will be treating both addiction and other medical problems, than for addiction specialists, who do not function as a patient’s primary care physician. In the primary care setting, practitioners may need to maintain two separate records for patients receiving general medical care and substance abuse treatment.
Treatment with immunotherapies, especially by active vaccination, has the potential to lead to long-term detectability because of markers in a person’s blood or urine. The ability to detect these markers—in the absence of a universal vaccination program—may lead to discrimination in a number of settings, including employment and health insurance. The potential of determining that someone was treated with a medication that is designed to block the effects of licit or illicit drugs may dissuade people from receiving the medication because of the potential for discriminatory treatment. This, too, is an issue that should be a focus of future research by NIDA.
There are some laws that bar discrimination because of past alcohol or drug use. For instance, the Americans with Disabilities Act of 1990 (ADA) prohibits employers from discriminating against employees who are in recovery from drug and alcohol problems. This protection afforded by the ADA does not cover employees and applicants who currently use illegal drugs, with testing for current illegal drug use not restricted. It is unclear, however, whether an employer can refuse to rehire an employee who was initially fired for an alcohol or drug problem but who is now clean and sober. In fact, the U.S. Supreme Court is considering this specific issue at the time of this writing, with a decision expected within the next year (see Raytheon v. Hernandez, 2003). This blanket no-rehire policy, if allowed to stand, is likely to have some effect on the willingness of individuals to be treated with immunotherapies that can leave a long-term biological marker, which carries the potential for detectability.
The use of immunotherapies and sustained-release formulations for addiction treatment in primary care medical settings raises important research questions. They include determination of the most effective models for integrating behavioral therapies into primary medical settings; developing empirical support for strategies to educate physicians and primary care practices in optimal addiction management strategies; developing standards to facilitate appropriate management of privacy issues; and the development and evaluation of mechanisms to finance integrated medical and psychosocial and behavioral services.
Given the substantial barriers to implementation of these treatments, special consideration should be given to supporting research on the most effective ways to facilitate dissemination of immunotherapies and sustained-release formulations to medical and addiction treatment systems. In addition, health services research evaluating the effects of various organizational and financial models for delivering these new therapies will be necessary to understand how structural factors influence treatment access, cost, and outcomes. We believe that these finance issues, in particular, will be extremely important for making these medications available, should they be proven to be safe and effective. The absence of sufficient financing can mitigate the effects of any improvements in the other philosophical and organizational issues we noted above.
PREVIOUS PHARMACOTHERAPIES LESSONS LEARNED
In addition to the issues discussed above, some of the medications that are currently available for treating substance use disorders have also faced impediments to their use. Here we review impediments to some medications that are currently available.
Weak efficacy (Krystal et al., 2001) or poor patient acceptance (Greenstein et al., 1981)—or both—have been a serious limitation for some of the medications currently available to treat substance use disorders. Examples of weak efficacy include naltrexone for alcohol dependence. While 15 well-designed studies have shown a naltrexone effect in reducing alcohol relapse, the largest study, which was a multisite study done in the Veterans Healthcare Administration (VHA) system, showed no effect in comparison with a placebo (Krystal et al., 2001). As there are many VHA providers who are physicians and might prescribe naltrexone, this study was particularly damning for its use within the largest physician-based substance abuse treatment setting. Naltrexone for opioid dependence also perhaps best exemplifies poor patient acceptance. Less than 15 percent of heroin addicts will agree to use this phar-
macologically highly effective medication that blocks heroin completely, with minimal side effects or other drug interactions. Similar issues of weak efficacy have diminished the use of nicotine replacement therapies and buproprion for smoking cessation. The availability of these medications, which counteract the pharmacologic effects of opioids, has not obviated the need for concomitant psychosocial and behavioral treatment to help users manage the craving and drug-seeking behavior that can also serve as cues for relapse.
Impediments to Opioid Pharmacotherapy
Specific factors also have influenced the success and failure for pharmacotherapy of different abused substances. Loitering and drug dealing in the vicinity of methadone clinics has resulted in strong community opposition to new opiate agonist programs (Genevie et al., 1988). Federal and state regulations have limited treatment access by restricting methadone dispensing to certain locations and applying criminal penalties for failure to comply with the regulations. The wording of these regulations has made many health care providers hesitant to get involved. Political opposition has also been quite explicit. The statements made by former New York City Mayor Rudolph Giuliani when he wanted to close all the methadone programs in New York City in 1998 clearly illustrate such opposition: “I think methadone is an enslaver. It’s a chemical that’s used to enslave people” (Swarns, 1998).
The wording of the Addiction Free Treatment Act of 1999 also reflected an ideological bias against substitution therapy and, apparently, misunderstanding of the background, rationale, and substantial efficacy of long-term methadone and LAAM substitution treatment. Wording in the act noted that “heroin addicts and methadone addicts are unable to function as self-sufficient, productive members of society … ” and concluded that the Congress needed to “work … to develop an effective drug control policy that … is based on detoxification and the comprehensive treatment of the pathology of drug addiction.” These assertions failed to recognize that patients who are on methadone are often able to function and to be productive members of society and able to take care of themselves. The act also failed to recognize that drug treatment usually results in reductions in drug use and criminal behavior, as well as increases in employment and other prosocial activities, such as paying taxes.
The opiate antagonist naltrexone has different reasons for its very modest success in treating opioid dependence. Because it has no agonist properties, it is not well liked by patients (Mark et al., 2000). Environmental factors also may play a role. Current studies in Russia have demonstrated much higher levels of interest by patients in naltrexone treatment than
has been seen in U.S. trials. The environmental factors at play in Russia appear to be the unavailability of agonist treatments, such as methadone, and the relatively young age of heroin addicts (about 22 years old on average) with strong family ties to their parents. These parents, particularly mothers, are willing to apply strict behavioral limits to these predominantly young men in order to ensure adherence with naltrexone ingestion. Substantial success with naltrexone has also been described in similarly structured family programs in the United States (Kosten et al., 1983). As long as naltrexone is taken, it is pharmacologically effective: thus, success with these medications may depend as much on behavioral intervention as it does on the medication itself. The key to success appears to be an appropriate match between the medication and the behavioral intervention.
Impediments to Alcohol Pharmacotherapies
Naltrexone for alcohol dependence has different reasons for poor success, including many of the reasons detailed above for pharmacotherapy failure in general, including staff reliance on psychosocial treatment rather than medications, lack of medical personnel to prescribe the medication, and ideology. The common ideology is that using naltrexone will undermine a drug-free life style. Cost is also a major issue, because naltrexone medication costs about $150 per month and is often not covered by insurance or public assistance programs. Initially it was also not covered by the VHA, although coverage is now provided. Thus, a person has to have a significant commitment to abstinence, and the available resources, in order to buy the medication.
Successes of Nicotine Pharmacotherapies
Nicotine replacement therapies and buproprion have been successful when adhered to, and in their financial returns to the manufacturers. Smoking, like most addictions, is a chronic relapsing disease, and individuals typically make many attempts to stop smoking. With each attempt, these medications can be obtained either by prescription from a primary care physician or simply purchased over the counter. This easy availability has led to good patient acceptance of these medications, relatively widespread use, and substantial financial returns to providers and manufacturers.
However, the movement to over-the-counter sales using a relatively low dose and shorter-acting version of the anti-nicotine patch has been associated with less success than the higher-dose medications that are prescribed by physicians (Thorndike, Biener, and Rigotti, 2002). This reduced
success may also reflect the greater likelihood of getting a physician’s advice to quit and concurrent behavioral interventions when nicotine replacement therapy is given by prescription.
The successful dissemination of these anti-addiction treatments was probably due to a variety of factors, including direct-to-consumer advertisements, substantial drug detailing by pharmaceutical representatives, good general publicity about their safety and utility, and aggressive education campaigns and tobacco control measures (e.g., smoking bans). We suspect that another potentially important factor, particularly in the marketing of nicotine replacement therapy, has been keeping the target population as adults with serious dependence on nicotine and not attempting to target adolescents who may be early in their tobacco smoking career. There are few data documenting the prevalence of nicotine replacement therapy among adolescents. One study involving more than 4,000 high school students found that only 5 percent had ever used either nicotine gum or patches (Klesges et al., 2003). Other studies have similarly documented low rates of nicotine replacement therapy by adolescents (Price et al., 2003; Lawrance 2001). Although it might be argued that adolescents would be more responsive to this treatment because they have less strongly ingrained habits (U.S. Department of Health and Human Services, 2000), the risks of these medications have generally been viewed as greater than these potential benefits. This “lesson” of not targeting adolescents may also be relevant to the new immunotherapies, where the goal might be to “protect” them from nicotine or other drug dependences even before they have any exposure. As we noted above regarding adolescents’ use of illegal drugs, adolescents do not appear to smoke because of the pharmacologic effects of nicotine. As some researchers have noted (Pierce, Farkas, and Evans, 1993; Sargent, Mott, and Stevens, 1998), adolescent smoking seems to be more opportunistic, with the continuous delivery of nicotine transdermally potentially serving to increase dependence in some cases.
The example of anti-nicotine therapies provides an interesting case for study (Lagrue, 1999). Whether a similar confluence of helpful factors can be brought to bear on other addictions and the newly developing immunotherapies and sustained-release medications remains to be examined, particularly since nicotine addiction is difficult to treat and even though it has quite modest success rates at continuous abstinence.
The application of new medications for addiction treatment must address the current clinical, organizational, and financial barriers that separate primary medical care and addiction treatment services. Research will have to address a number of questions and their policy implications related to adequate financing of the medications and associated psychosocial and behavioral services; improved linkages between primary care
and specialty treatment, perhaps as one of a number of ways of allowing for the provision of medication and adjunct services and identifying best practices; and the appropriate education of providers, professional organizations, and the public to challenge some of the philosophical and other biases that may limit the usefulness of these therapies. The overall outcome of this research may be to identify what package of psychosocial and behavioral services (e.g., composition, approach, duration, amount, and practitioner type) needs to be linked with the different types of medications to achieve good patient outcomes.
The financing of these medications also needs further research. Again, we emphasize how centrally important these issues are to making immunotherapies and depot medications available. Financing is especially important because immunotherapies, in particular, are likely to have substantial initial costs. Consequently, it may be useful for NIDA to support health services research on how various public and private organizational and financing models for addiction medication delivery affect treatment access, cost, and outcomes.
Recommendation 4 The National Institute on Drug Abuse should support studies of whether the potential for discrimination due to long-lasting markers in the blood or urine deters people with drug dependence from accepting immunotherapies. The effects of immunotherapies on false-positive and false-negative drug testing results should also be studied.
Recommendation 5 The National Institute on Drug Abuse should support clinical effectiveness studies and financing models that integrate the new pharmacotherapies with psychosocial services in specialty and primary medical care settings.
COST AND ECONOMIC ISSUES
One of the primary reasons for looking at the introduction of new immunotherapies from an economic perspective is their high prospective cost and the belief by many experts that substance abuse treatment is already underfunded. There are other economic issues—issues that can be informed by economic theory and analysis—in considering the therapies and how they might interact with patients’ behavior. This section considers three such issues, but we note that it is only suggestive of the types and complexities of economic issues for immunotherapies:
the cost of these new therapies;
the sensitivity of clients to the degree of effectiveness of the therapy; and
the cost effectiveness of immunotherapies and sustained-release formulations.
After safety and efficacy have been established with immunotherapies and sustained-release formulations, the cost of these new therapies will have to be examined. Cost information will be essential for determining the prospective expense of making immunotherapies available, and it is highly likely to affect whether and how individuals use these therapies. Studies have shown that consumers are sensitive to the cost and cost-sharing of behavioral health services (Sturm, Goldman, and McCulloch, 1998), while public and private payers are equally attuned to, and resistant to, the costs associated with delivering these services. As discussed by Thomas and McCarty (this volume) new substance abuse treatment medications in the past decade have been slow to be accepted for reimbursement by public treatment systems or private insurance carriers.
There are only a very few monoclonal antibody immunotherapy products now on the market that are analogous to the proposed therapies; they appear to cost in the range of $1,500 to $2,000 per administration or infusion (Kosten and Kranzler, this volume). It is expected that a single administration of monoclonal antibodies will be effective for up to several months (Pentel, this volume). Moreover, patients are likely to need or want to have several courses of therapy due to the ongoing risk of relapse. It is unknown how costs might be affected if monoclonal antibodies for two or more drugs (e.g., methamphetamine and PCP) are infused simultaneously.
In contrast, vaccines and depot preparations currently under development tend to cost an order of magnitude less per administration (an injection delivered under medical supervision), and it seems likely that a patient will need to have injections every several months to maintain adequate levels of effectiveness. Because the field of immunotherapy is working to develop lower-cost methods of producing monoclonal antibodies, it may be important to examine and monitor cost trends for these classes of therapies.
Sensitivity of Clients to Effectiveness
While it is expected that complete effectiveness of these therapies (defined as blocking any psychoactive effects) will rapidly bring a compliant patient to near or complete cessation of the use of the targeted substance, current research indicates that the immunotherapies will only be partially effective (see Pentel, this volume). Patients that take the
“blocked” substances may get different degrees of (attenuated) psychoactive effects. Consequently, variations in effectiveness across patients—and why, as well as how, this can be optimized—and different patient’s responses to different levels of effectiveness may be important to examine (National Research Council, 2001). As noted above, it is known that the effectiveness of immunotherapies to block psychoactive effects decreases over time.
In an economic sense, a therapy with low to modest ability to attenuate psychoactive effects could be modeled and thought of as a price increase for the drug in question (see Kleiman, this volume). Absent psychosocial or other interventions (such as testing and sanctions) the effectiveness of the immunotherapy or sustained-release formulation might be comparable in magnitude to an increase in the retail (or street) price of the drug.
Cigarette smokers who use low nicotine products have been observed to increase their consumption (use more cigarettes per day or inhale more deeply) to maintain their dosage of nicotine (and as an unintended consequence, quite possibly their intake of tar and other cigarette byproducts) (Kozlowski et al., 1996). Users of illicit drugs are known to be highly sensitive to the “quality” (e.g., purity or concentration of the active ingredient) of the drug consumed and adjust their consumption of the drug in a manner that regulates the dosage received. Thus, it is quite possible that a low efficacy medication may see continued use and even increased use by some patients, with possible adverse consequences for the individual (e.g., from harms such as HIV/HCV infection that are associated with administration not intoxication) and for society (e.g., from increased demand that stimulates increases in drug-related crime) (Kleiman, this volume).
The central economic fact of all health care is that resources are scarce and potential demands are virtually unlimited. Consumers, society, and the health system confront the fundamental economic question of how to optimize well-being in the face of scarce resources (Gold et al., 1996). The publicly subsidized substance abuse treatment system is well known to face limited financing, leading to waiting lists for clients and competition between providers and different types of care for resources (Center for Substance Abuse Treatment, 2000). Private and public insurance plans generally have limited coverage for substance abuse treatment therapies and medications. Cost effectiveness analysis can offer insights on the relative value of alternative health interventions.
Public and private purchasers of treatment will need to carefully consider how the benefits and costs of immunotherapies and depot medica-
tions compare with alternative, existing treatment approaches, as well as with other health services. Cost effectiveness analysis might be useful, as part of the clinical trial process, to provide potential purchasers and consumers with information that can be used in making financing decisions. To date, such analysis has had few applications in treatment for tobacco and drug abuse. Particular challenges are posed by substance abusers and the nature of the disorder that will need to be addressed, which include the fact that illicit drug and tobacco use often occurs over a number of years, with some effects occurring during the use period, while others may be delayed by many years. In addition, individuals are at risk of relapse (and, perhaps, reinitiated treatment) for a number of years. Another issue is that many of the consequences of drug use of most concern to communities are “externalities”—that is, the affects on the families of smokers and drug users, victims of crimes committed by drug users, and victims of disease transmitted by drug users.
Nonetheless, application of this decision methodology has spread rapidly throughout the general health field. Those responsible for making funding and purchasing decisions in health plans and those developing clinical practice guidelines will have an increasing need for cost effectiveness data.