National Institute on Alcohol Abuse and Alcoholism No. 17 PH 322 July 1992

Treatment Outcome Research

Treatment outcome research is designed to answer six basic questions: Is treatment better than no treatment? Is treatment worse than no treatment? Is one treatment better than another? If a treatment is effective, is a little just as good as a lot? Does quality of life change because drinking has changed? Are the benefits of treatment worth the cost? Although no single study is likely to answer all of these questions, every medical and behavioral treatment needs to be evaluated along these lines.

Until the last decade, alcoholism treatment research lagged behind standard medical and behavioral treatment research. Randomized controlled trials, the most objective type of treatment research methodology, were rarely used by alcohol treatment researchers. Instead, much of the early research suffered from lack of comparison groups, high rates of attrition, and reliance solely on self-reports of alcohol consumption, all of which may have biased, or skewed, the results.

Methodology

Controlled trials. Controlled clinical trials have become a widely accepted method for evaluating treatment with the least bias (1). This method uses comparison groups, known as controls, that receive either no treatment or a treatment different from the treatment under study. Researchers evaluate treatment effectiveness by comparing patient outcome in the study group to patient outcome in the control group.

Randomization. Differing patient characteristics can influence the outcome of research--some patients are more motivated to recover, some are sicker than others, some have more social support. To distribute these characteristics evenly among comparison groups, researchers place patients in groups at random, a method known as randomization. Such randomization produces treatment groups that are likely to be equivalent in every aspect but the treatment itself.

Blinding. Double-blind studies, in which both evaluators and patients are unaware of which patients receive which treatments, keep research results objective (1). When testing medications, neither patients nor evaluators can distinguish between a placebo and the actual medication. However, with verbal therapies (common in most alcoholism treatments), only the evaluators can be blinded.

Followup. A well-done study follows up all participants, including those who drop out of the study. Following only patients who remain in a study may exaggerate the effectiveness of a particular treatment because those who drop out usually do so because they have relapsed. How long study participants should be followed is a matter for debate. Because most relapse tends to occur within the first 6 months after the completion of treatment, some argue that a 6-month followup is sufficient. Others contend that patients should be followed for as long as 2 years. The duration of followup usually is determined by the objective of the study and the financial resources available to support the study.

Outcome measures. To assess treatment effectiveness, researchers use a variety of outcome measures, including patient self-reports, to gauge changes in drinking behavior, physical health status, psychological health status, and social functioning. These measures must be valid and consistent. Because patient self-reports may be inaccurate, some researchers recommend that the reports be verified by relatives or friends close to the patient and/or by periodic laboratory testing of urine, blood, or breath alcohol levels (2). Because alcohol remains in body fluids less than 12 hours, a laboratory test that could measure long-term alcohol consumption is needed. Efforts to develop such a test are in progress. Cu rrently, the serum gamma-glutamyltransferase (GGT) is being used successfully by some researchers to corroborate patient self-reports (3).

Where Is Research Needed?

Many commonly used treatments have not been adequately evaluated and need to undergo controlled clinical trials. These trials will not only verify the effectiveness of treatment but also may help to improve outcome and cost-effectiveness. The highly regarded approach to alcoholism, Alcoholics Anonymous (AA), has proved difficult to evaluate. Part of the problem stems from the difficulty of studying AA under natural conditions and the inability to randomize patient samples due to the AA tradition of member anonymity (4). A popular treatment approach, the inpatient "Minnesota Model," uses a philosophy of self-help similar to that of AA (5). The program combines referral to AA both during inpatient treatment and as part of an aftercare program. The model relies heavily on counseling (both personal and family). Few controlled studies have been conducted on the model's effectiveness (6,7); however, two recent studies, one in the United States (8) and one in Finland (9), support its effectiveness.

Inpatient Versus Less Intensive Treatment: What Does Treatment Outcome Research Reveal?

The effectiveness of inpatient versus less intensive treatment continues to be debated and studies have been conducted comparing the two at all stages of recovery. In a well-designed randomized study, Hayashida and colleagues compared detoxification using benzodiazepines in an inpatient setting and in an outpatient setting and found no difference in outcome between the two (10). After detoxification, treatment for long-term recovery can begin. One study compared outcome of an inpatient alcoholism treatment program with outcome of a day hospital program and found that the intensive outpatient treatment was as effective as the inpatient treatment (11). In a controlled clinical trial, Walsh and colleagues compared hospitalization (including AA) with AA alone for employees at risk of job loss (8). Results of this study suggest that inpatient rehabilitation produces a more effective outcome than AA alone. Although these individual studies cannot be compared directly with one another because they examine quite different treatments, together they serve as a basis for other controlled studies investigating intensive versus less intensive treatment.

Treatment outcome research has provided evidence that other treatments may help reduce drinking among recovering alcoholics. These include behavioral training such as stress management therapy, assertiveness and communication skills training, behavioral self-control training, and behavioral marital therapy. One controlled clinical trial found that social skills training decreased the duration and severity of relapse after 1 year in a group of alcoholics (12). Research has been done on acupuncture therapy; however, two recent studies have produced conflicting results (13,14).

Medications

Two types of medications have been introduced to reduce drinking: one to deter drinking and another to reduce the craving for alcohol. A large body of outcome research addresses the use of disulfiram, a medication that deters drinking. Many studies have reported favorable results, but most were methodologically flawed. More recent, better designed studies have not replicated the results of earlier studies. Fuller and colleagues (15) conducted a well-controlled clinical trial examining the efficacy of disulfiram. Patients were placed in one of three groups at random: a treatment group, receiving a daily 250 mg dose of disulfiram; and two control groups, one receiving a daily 1 mg dose of disulfiram and the other receiving a vitamin in place of disulfiram. Patients were followed up seven times over a 1-year period and outcome was measured with self-reports corroborated by interviews with relatives or friends, and by blood an d urine tests (15). Although there was no significant difference among the three groups in terms of total abstinence, the group receiving the 250 mg of disulfiram reported significantly fewer drinking days than the other two groups. Another controlled study found disulfiram to be most effective for married patients when their spouses attempted to ensure that they took their medication (16).

Treatment outcome research has examined a wide range of other medications, including antidepressants and lithium. Studies are investigating lithium's effectiveness in treating alcoholism, independent of its effect on manic depression (i.e., Does lithium treat alcoholism by treating depression, or does it have a direct effect on drinking behavior?). However, a well-designed study (17) found lithium ineffective in treating alcoholics without manic-depressive syndrome.

Other studies are investigating promising new pharmacotherapies. In preliminary studies, the opiate antagonist, naltrexone, appears to reduce the frequency of relapse (18,19). If replicated, such research may lead to pharmacotherapy becoming integral to alcoholism rehabilitation.

Increasing Efficiency Through Outcome Research

Research has shown that alcoholism is a heterogeneous disease that may require multiple methods of treatment (20). Treatment that works well for one type of alcoholic may not work for another.

Traditionally, alcoholism treatment programs have offered patients a mix of treatment approaches. A promising new strategy involves matching patients to interventions more specific to their needs. Determining which patients respond best to which treatments can increase treatment effectiveness. A wide range of patient-treatment matching effects have already been reported (21).

Efficiency and cost of alcoholism treatment are important considerations for many patients, third-party payers, and clinics deciding on a treatment type. As outcome research distinguishes effective from ineffective treatments, judgments can begin to be made based on cost (7).

Treatment Outcome Research--A Commentary by
NIAAA Director Enoch Gordis, M.D.

While treatment outcome research is not a new idea, it is fairly new in the alcohol field. Just as it would be unthinkable to unleash a new drug therapy for cancer, a new antibiotic for kidney

disease, or a new contraceptive without scientific evidence of safety and efficacy, treatments for alcoholism must be rigorously evaluated to ensure that patients get the best help possible.

Treatment outcome studies are designed to answer commonsense questions. To determine whether a treatment accomplishes anything, we have to know how patients who have not received the treatment fare. Perhaps untreated patients do just as well, implying that the treatment does not influence outcome at all. Or, perhaps treated patients do worse.

Research can provide information that could help reduce the cost and inconvenience of treatment to patients. If the treatment is helpful, a little bit of it may be as useful as a lot. We must also determine whether a treatment that appears effective under ideal circumstances (e.g., good patient compliance and well-trained staff) will work under "real world" conditions (crowded clinics, varying levels of staff training, and poor patient compliance).

Treatment outcome research will support new approaches; alcoholism treatment providers must take the time to keep up with and apply the results of research in their programs or practice. Simply put, there is nothing sacred about any of today's treatment methods. For any disease, we hope that tomorrow's treatment will be better than today's. The experience and wisdom of the

many caring, competent, and dedicated alcoholism treatment personnel will continue to be key ingredients in alcoholism treatment. However, new treatment technologies o r techniques will improve patient outcome, and it is important that treatment providers stay abreast of new developments.

References

(1) FULLER, R.K. Controlled clinical trials. Alcohol Health & Research World 14(3):239-244, 1990. (2) FULLER, R.K.; Lee, K.K.; & Gordis, E. Validity of self-report in alcoholism research: Results of a Veterans Administration cooperative study. Alcoholism: Clinical and Experimental Research 12(2):201-205, 1988 (3) IRWIN, M.; Baird, S.; Smith, T.; & Schuckit, M. Use of laboratory tests to monitor heavy drinking by alcoholic men discharged from a treatment program. American Journal of Psychiatry 145(5):595-599, 1988. (4) MCBRIDE, J.L. Abstinence among members of Alcoholics Anonymous. Alcoholism Treatment Quarterly 8(1):113-121, 1991. (5) COOK, C.C.H. The Minnesota Model in the management of drug and alcohol dependency: Miracle, method or myth? Part I. The philosophy and the programme. British Journal of Addiction 83(6):625-634, 1988. (6) COOK, C.C.H. The Minnesota Model in the management of drug and alcohol dependency: Miracle, method, or myth? Part II. Evidence and conclusions. British Journal of Addiction 83(7):735-748, 1988. (7) HOLDER, H.; Longabaugh, R.; Miller, W.R.; & Rubonis, A.V. The cost effectiveness of treatment for alcoholism: A first approximation. Journal of Studies on Alcohol 52(6):517-540, 1991. (8) WALSH, D.C.; Hingson, R.W.; Merrigan, D.M.; Levenson, S.M.; Cupples, L.A.; Heeren, T.; Coffman, G.A.; Becker, C.A.; Barker, T.A.; Hamilton, S.K.; McGuire, T.G.; & Kelly, C.A. A randomized trial of treatment options for alcohol-abusing workers. New England Journal of Medicine 325(11):775-782, 1991. (9) KESO, L., & Salaspuro M. Inpatient treatment of employed alcoholics: A randomized clinical trial on Hazelden-type and traditional treatment. Alcoholism: Clinical and Experimental Research 14(4):584-589, 1990. (10) HAYASHIDA, M.; Alterman, A.I.; McLellan, A.T.; O'Brien, C.P.; Purtill, J.J.; Volpicelli, J.R.; Raphaelson, A.H.; & Hall, C. Comparative effectiveness and costs of inpatient and outpatient detoxification of patients with mild-to-moderate alcohol withdrawal syndrome. New England Journal of Medicine 320:358-365, 1989. (11) LONGABAUGH, R.; McCrady, B.; Fink, E.; Stout, R.; McAuley, T.; Doyle, C.; & McNeill, D. Cost effectiveness of alcoholism treatment in partial vs inpatient settings: Six-month outcomes. Journal of Studies on Alcohol 44(6):1049-1071, 1983. (12) CHANEY, E.F.; O'Leary, M.R.; & Marlatt, G.A. Skill training with alcoholics. Journal of Consulting and Clinical Psychology 46(5):1092-1104, 1978. (13) BULLOCK, M.L.; Culliton, P.D.; & Olander, R.T. Controlled trial of acupuncture for severe recidivist alcoholism. Lancet 1(8652):1435-1439, 1989. (14) WORNER, T.M. ; Zeller, B.; Schwarz, H.; Zwas, F.; & Lyon, O. Acupuncture fails to improve treatment outcome in alcoholics. Drug and Alcohol Dependence 20(2):169-173, 1992. (15) FULLER, R.K.; Branchey, L.; Brightwell, D.R.; Derman, R.M.; Emrick, C.D.; Iber, F.L.; James, K.E.; Lacoursiere, R.B.; Lee, K.K.; Lowenstam, I.; Maany, I.; Neiderhiser, D.; Nocks, J.J.; & Shaw, S. Disulfiram treatment of alcoholism: A Veterans Administration cooperative study. Journal of the American Medical Association 256(11):1449-1455, 1986. (16) AZRIN, N.H.; Sisson, R.W.; Meyers, R.; & Godley, M. Alcoholism treatment by disulfiram and community reinforcement therapy. Journal of Behavior Therapy and Experimental Psychiatry 13:105-112, 1982. (17) DORUS, W.; Ostrow, D.; Anton, R.; Cushman, P.; Collins, J.F.; Schaefer, M.; Charles, H.L.; Desai, P.; Hayashida, M.; Malkerneker, U.; Willenbring, M.; Fiscella, R.; & Sather, M.R. Lithium treatment of depressed and non-depressed alcoholics. Journal of the American Medical Association 262(12):1646-1652, 1989. (18) VOLPICELLI, J.R.; O'Brien, C.P.; Alterman, A.I.; & Hayashida, M. Naltrexone and the treatment of alcohol-dependence: Initial observations. In: Reid, L.D., ed. Opioids, Bulimia and Alcohol Abuse and Alcoholism. New York: Springer-Verlag, 1990. pp. 195-214. (19) O'MALLEY, S.S.; Jaffe, A.; Chang, G.; Witte, G.; Schottenfeld, R.S.; & Rounsaville, B.J. Naltrexone in the treatment of alcohol dependence: Preliminary findings. In: Naranjo, C.A., and Sellers, E.M., eds. Novel Pharmacological Interventions for Alcoholism. New York: Springer-Verlag, 1992. pp. 148-160. (20) GRANT, B.F.; CHOU, S.P.; Pickering, R.P.; & Hasin, D.S. Empirical subtypes of DSM-III-R alcohol dependence: United States, 1988. Drug and Alcohol Dependence 30(1):75-84, 1992. (21) MATTSON, M.E., & Allen, J.P. Research on matching alcoholic patients to treatments: Findings, issues, and implications. Journal of Addictive Diseases 11(2):33-49, 1991.

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