More research is needed to investigate variables that may moderate the effects of reinforcement-based interventions. The efficacy of reinforcement- based interventions is determined, in part, by quantitative and qualitative features of the reinforcers, including reinforcer magnitude, frequency, and delay (see Meredith et al., 2014). Petry et al. (2012) found reinforcement- based medication adherence interventions that utilized greater magnitudes of reinforcement and more frequent reinforcement engendered larger effect sizes. This finding is consistent with results of research in other domains (e.g., Lussier et al., 2006). However, few prospective studies have been conducted to evaluate the effects of these variables on medication adherence.
Although one such study conducted by Carroll et al. (2002) found no effect of reinforcer magnitude on medication adherence, this study compared only two different magnitudes of reinforcement.
Much more research is needed on the effects of reinforcement-based
interventions on secondary health outcomes. In patients who are moderately adherent to certain medications (e.g., antiretroviral therapy), minor increases in adherence may produce health benefits (e.g., suppression of viral replication). Thus, major increases in adherence like those observed in most studies discussed in this chapter would certainly be expected to have clinically meaningful effects on health. Although some studies reviewed in this chapter found reinforcement of medication adherence was associated with improvements in biological indices of health (e.g., Rosen et al., 2007), other studies were not powered to detect changes in secondary outcomes (e.g., Petry et al., 2015), or they did not report any health-related outcomes other than adherence (e.g., Cass et al., 2005).
More research is needed on the post-treatment effects of reinforcement- based interventions on medication adherence. Although post-treatment effects are of little concern when a medication regimen is of short duration (e.g., for acute health conditions), they are of major concern when the regimen lasts substantially longer than the intervention (e.g., for chronic health conditions).
Yet, only a handful of studies have investigated post-treatment effects of reinforcement-based interventions on adherence, and these studies showed treatment effects diminished over time (e.g., Rosen et al., 2007). Indeed, long-term treatment efficacy is the Achilles’ heel of virtually every behavioral, psychosocial, or pharmacological intervention designed to treat a chronic health problem. Treatment effects typically dissipate when interventions are terminated. However, this pattern may be changed within the context of reinforcement-based interventions by adopting affordable strategies to extend treatment duration (e.g., schedule thinning; Preston et al., 2002). Indeed, research suggests increasing treatment duration prolongs treatment effects (Petry et al., 2012).
Research is critically needed to evaluate the cost-effectiveness of reinforcement-based interventions, particularly those designed to promote adherence in patients with chronic diseases. Interventions of considerable duration and, therefore, substantial cost, may be required to treat these patients. Although researchers have developed strategies to minimize or offset the costs associated with reinforcement-based interventions (e.g., Petry, 2000; Silverman et al., 2001), this type of intervention will always come with a price tag. Before implementing reinforcement-based interventions on a wide scale, key stakeholders and policymakers will want to know if the savings in health care costs that result from improved adherence will cover
the costs associated with reinforcement-based interventions.
Finally, more research is needed on the acceptability of reinforcement- based interventions to promote medication adherence. Some critics of reinforcement-based interventions are morally opposed to paying patients to do something they believe the patients should be motivated to do on their own (Parke et al., 2013). However, research shows these objections vary considerably depending on the targeted behavior. For example, taxpayers may object more to reinforcement-based interventions that promote smoking cessation compared to those that promote compliance with mental health therapy (Promberger et al., 2011). The extent to which these objections apply to interventions that promote medication adherence is unclear.
Conclusion
The problem of medication nonadherence cannot be overstated. It is a global epidemic. Although many of the solutions that have been proposed to combat this public health threat are complex, the issue itself is as simple as former U.S. Surgeon General C. Everett Koop once put it, “Drugs don’t work in patients who don’t take them.”
This simple problem has a promising, evidence-based solution:
reinforcement-based interventions. However, there are research gaps, financial concerns, logistical challenges, and ethical objections associated with these interventions. More research is needed on the long-term effects of reinforcement-based interventions on adherence and health. Data on the cost- effectiveness of these interventions are needed. New procedures and better technology are needed to facilitate remote, objective assessment of adherence. Ethical decisions regarding which patients should benefit from reinforcement-based interventions must also be considered.
Until these issues are addressed, they will likely function as barriers to the large-scale adoption of reinforcement-based interventions to promote medication adherence. However, because researchers, practitioners, and policymakers in other domains have found ways to circumvent many of the same barriers (e.g., Petry et al., 2014), there is reason to remain optimistic about the dissemination potential of reinforcement-based interventions to promote medication adherence.
Just as there is reason for optimism, there is also reason for urgency. As
the literature reviewed in this chapter suggests, reinforcement-based interventions are feasible, flexible, and powerful interventions that produce robust improvements in medication adherence. The sooner these interventions can be translated from research into practice, the sooner they can be used to improve the health and well-being of millions of nonadherent patients around the world.
Acknowledgments
Preparation of this chapter was supported in part by National Institutes of Health grants P50-DA09241, P60-AA03510, R01-HD075630, and DP3- DK097705.
References
Bouvy, M.L., Heerdink, E.R., Urquhart, J., Grobbee, D.E., Hoe, A.W., and Leufkens, H.G. (2003). “Effect of a Pharmacist-led Intervention on Diuretic Compliance in Heart Failure Patients: A Randomized Controlled Study,” Journal of Cardiac Failure 9(5): 404–411.
Brown, M.T. and Bussell, J.K. (2011). “Medication Adherence: WHO Cares?” Mayo Clinic Proceedings 86(4): 304–314.
Carroll, K.M., Sinha, R., Nich, C., Babuscio, T., and Rounsaville, B.J.
(2002). “Contingency Management to Enhance Naltrexone Treatment of Opioid Dependence: A Randomized Clinical Trial of Reinforcement Magnitude,” Experimental and Clinical Psychopharmacology 10(1): 54.
Cass, A., Talavera, G., Gresham, L., Moser, K., and Joy, W. (2005).
“Structured Behavioral Intervention to Increase Children’s Adherence to Treatment for Latent Tuberculosis Infection,” The International Journal of Tuberculosis and Lung Disease 9(4): 415–420.
Centers for Disease Control and Prevention (2015). “Therapeutic Drug Use.”
Available at http://www.cdc.gov/nchs/fastats/drug-use-therapeutic.htm (accessed January 29, 2016).
Chernew, M.E., Rosen, A.B., and Fendrick, A.M. (2007). “Value-based Insurance Design,” Health Affairs 26(2): 195–203.
Cramer, J.A. and Rosenheck, R. (1998). “Compliance with Medication
Regimens for Mental and Physical Disorders,” Psychiatric Services 49(2):
196–201.
DeFulio, A. and Silverman, K. (2012). “The Use of Incentives to Reinforce Medication Adherence,” Preventive Medicine 55: S86–S94.
DeFulio, A., Everly, J.J., Leoutsakos, J.S., Umbricht, A., Fingerhood, M., Bigelow, G.E., et al. (2012). “Employment-based Reinforcement of Adherence to an FDA Approved Extended Release Formulation of Naltrexone in Opioid-dependent Adults: A Randomized Controlled Trial,”
Drug and Alcohol Dependence 120(1): 48–54.
DiMatteo, M.R. (2004). “Variations in Patients’ Adherence to Medical Recommendations: A Quantitative Review of 50 Years of Research,”
Medical Care 42(3): 200–209.
Dunn, K.E., Defulio, A., Everly, J.J., Donlin, W.D., Aklin, W.M., Nuzzo, P.A., et al. (2013). “Employment-based Reinforcement of Adherence to Oral Naltrexone Treatment in Unemployed Injection Drug Users,”
Experimental and Clinical Psychopharmacology 21(1): 74.
Elk, R., Grabowski, J., Rhoades, H., Spiga, R., Schmitz, J., and Jennings, W.
(1993). Compliance with Tuberculosis Treatment in Methadone- maintained Patients: Behavioral Interventions, Journal of Substance Abuse Treatment 10(4): 371–382.
Farley, J.F., Wansink, D., Lindquist, J.H., Parker, J.C., and Maciejewski, M.L. (2012). “Medication Adherence Changes Following Value-based Insurance Design,” The American Journal of Managed Care 18(5): 265–
274.
Fischer, M.A., Stedman, M.R., Lii, J., Vogeli, C., Shrank, W.H., Brookhart, M.A., et al. (2010). “Primary Medication Non-adherence: Analysis of 195,930 Electronic Prescriptions,” Journal of General Internal Medicine 25(4): 284–290.
Goldman, D.P., Joyce, G.F., and Zheng, Y. (2007). “Prescription Drug Cost Sharing: Associations with Medication and Medical Utilization and Spending and Health,” JAMA 298(1): 61–69.
Haynes, R.B. (2001). “Interventions for Helping Patients to Follow Prescriptions for Medications,” Cochrane Database of Systematic Reviews, 1.
Higgins, S.T., Alessi, S.M., and Dantona, R.L. (2002). “Voucher-based Incentives: A Substance Abuse Treatment Innovation,” Addictive
Behaviors 27(6): 887–910.
Ho, P.M., Magid, D.J., Masoudi, F.A., McClure, D.L., and Rumsfeld, J.S.
(2006). “Adherence to Cardioprotective Medications and Mortality among Patients with Diabetes and Ischemic Heart Disease,” BMC Cardiovascular Disorders 6(1): 48.
Huskamp, H.A., Deverka, P.A., Epstein, A.M., Epstein, R.S., McGuigan, K.A., and Frank, R.G. (2003). “The Effect of Incentive-based Formularies on Prescription-drug Utilization and Spending,” New England Journal of Medicine 349(23): 2224–2232.
Kazdin, A.E. (1982). “The Token Economy: A Decade Later,” Journal of Applied Behavior Analysis 15(3): 431–445.
Keller, P.A., Harlam, B., Lowenstein, G., and Volpp, K.G. (2011).
“Enhanced Active Choice: A New Method to Motivate Behavior Change,”
Journal of Consumer Psychology 21: 376–383.
Kennedy, J., Tuleu, I., and Mackay, K. (2008). “Unfilled Prescriptions of Medicare Beneficiaries: Prevalence, Reasons, and Types of Medicines Prescribed,” Journal of Managed Care Pharmacy 14(6): 553–560.
Liebson, I.A., Tommasello, A., and Bigelow, G.E. (1978). “A Behavioral Treatment of Alcoholic Methadone Patients,” Annals of Internal Medicine 89(3): 342–344.
Lowe, C.J., Raynor, D.K., Purvis, J., Farrin, A., and Hudson, J. (2000).
“Effects of a Medicine Review and Education Programme for Older People in General Practice,” British Journal of Clinical Pharmacology 50(2):
172–175.
Lussier, J.P., Heil, S.H., Mongeon, J.A., Badger, G.J., and Higgins, S.T.
(2006). “A Meta-analysis of Voucher-based Reinforcement Therapy for Substance Use Disorders,” Addiction 101(2): 192–203.
Maciejewski, M.L., Farley, J.F., Parker, J., and Wansink, D. (2010).
“Copayment Reductions Generate Greater Medication Adherence in Targeted Patients,” Health Affairs 29(11): 2002–2008.
Meredith, S.E., Jarvis, B.P., Raiff, B.R., Rojewski, A.M., Kurti, A., Cassidy, R.N., et al. (2014). “The ABCs of Incentive-based Treatment in Health Care: A Behavior Analytic Framework to Inform Research and Practice,”
Psychology Research and Behavior Management 7: 103–114.
Minozzi, S., Amato, L., Vecchi, S., Davoli, M., Kirchmayer, U., and Verster, A. (2011). “Oral Naltrexone Maintenance Treatment for Opioid
Dependence,” Cochrane Database of Systematic Reviews 16.
Nieuwlaat, R., Wilczynski, N., Navarro, T., Hobson, N., Jeffery, R., Keepanasseril, A., et al. (2014). “Interventions for Enhancing Medication Adherence,” Cochrane Database of Systematic Reviews 11.
Osterberg, L. and Blaschke, T. (2005). “Adherence to Medication,” New England Journal of Medicine 353(5): 487–497.
Ottomanelli, G. (1999). “Methadone Patients and Alcohol Abuse,” Journal of Substance Abuse Treatment 16(2): 113–121.
Parke, H., Ashcroft, R., Brown, R., Marteau, T.M., and Seale, C. (2013).
“Financial Incentives to Encourage Healthy Behaviour: An Analysis of UK Media Coverage,” Health Expectations 16(3): 292–304.
Paterson, D.L., Swindells, S., Mohr, J., Brester, M., Vergis, E.N., Squier, C., et al. (2000). “Adherence to Protease Inhibitor Therapy and Outcomes in Patients with HIV Infection,” Annals of Internal Medicine 133(1): 21–30.
Petry, N.M. (2000). “A Comprehensive Guide to the Application of Contingency Management Procedures in Clinical Settings,” Drug and Alcohol Dependence 58(1): 9–25.
Petry, N.M., Alessi, S.M., Byrne, S., and White, W.B. (2015). “Reinforcing Adherence to Antihypertensive Medications,” The Journal of Clinical Hypertension 17(1): 33–38.
Petry, N.M., DePhilippis, D., Rash, C.J., Drapkin, M., and McKay, J.R.
(2014). “Nationwide Dissemination of Contingency Management: The Veterans Administration Initiative,” The American Journal on Addictions 23(3): 205–210.
Petry, N.M., Rash, C.J., Byrne, S., Ashraf, S., and White, W.B. (2012).
“Financial Reinforcers for Improving Medication Adherence: Findings from a Meta-analysis,” The American Journal of Medicine 125(9): 888–
896.
Piette, J.D., Weinberger, M., McPhee, S.J., Mah, C.A., Kraemer, F.B., and Crapo, L.M. (2000). “Do Automated Calls with Nurse Follow-up Improve Self-care and Glycemic Control among Vulnerable Patients with Diabetes?” The American Journal of Medicine 108(1): 20–27.
Preston, K.L., Silverman, K., Umbricht, A., DeJesus, A., Montoya, I.D., and Schuster, C.R. (1999). “Improvement in Naltrexone Treatment Compliance with Contingency Management,” Drug and Alcohol Dependence 54(2):
127–135.
Preston, K.L., Umbricht, A., and Epstein, D.H. (2002). “Abstinence Reinforcement Maintenance Contingency and One-year Follow-up,” Drug and Alcohol Dependence 67(2): 125–137.
Promberger, M., Brown, R.C., Ashcroft, R.E., and Marteau, T.M. (2011).
“Acceptability of Financial Incentives to Improve Health Outcomes in UK and U.S. samples,” Journal of Medical Ethics 37(11): 682–687.
Roll, J.M. and Higgins, S.T. (2000). “A Within-subject Comparison of Three Different Schedules of Reinforcement of Drug Abstinence Using Cigarette Smoking as an Exemplar,” Drug and Alcohol Dependence 58(1): 103–109.
Rosen, M.I., Dieckhaus, K., McMahon, T.J., Valdes, B., Petry, N.M., Cramer, J., and Rounsaville, B. (2007). “Improved Adherence with Contingency Management,” AIDS Patient Care and STDs 21(1): 30–40.
Sabaté, E. (2003). “Adherence to long-term therapies: Evidence for action,”
World Health Organization.
Seal, K.H., Kral, A.H., Lorvick, J., McNees, A., Gee, L., and Edlin, B.R.
(2003). “A Randomized Controlled Trial of Monetary Incentives vs.
Outreach to Enhance Adherence to the Hepatitis B Vaccine Series among Injection Drug Users,” Drug and Alcohol Dependence 71(2): 127–131.
Silverman, K., Svikis, D., Robles, E., Stitzer, M.L., and Bigelow, G.E.
(2001). “A Reinforcement-based Therapeutic Workplace for the Treatment of Drug Abuse: Six-month Abstinence Outcomes,” Experimental and Clinical Psychopharmacology 9: 14–23.
Simpson, S.H., Eurich, D.T., Majumdar, S.R., Padwal, R.S., Tsuyuki, R.T., Varney, J., et al. (2006). “A Meta-analysis of the Association between Adherence to Drug Therapy and Mortality,” BMJ 333(7557): 15.
Sokol, M.C., McGuigan, K.A., Verbrugge, R.R., and Epstein, R.S. (2005).
“Impact of Medication Adherence on Hospitalization Risk and Healthcare Cost,” Medical Care 43(6): 521–530.
Sorensen, J.L., Haug, N.A., Delucchi, K.L., Gruber, V., Kletter, E., Batki, S.L., et al. (2007). “Voucher Reinforcement Improves Medication Adherence in HIV-positive Methadone Patients: A Randomized Trial,”
Drug and Alcohol Dependence 88(1): 54–63.
Staring, A.B., Mulder, C.L., and Priebe, S. (2010). “Financial Incentives to Improve Adherence to Medication in Five Patients with Schizophrenia in the Netherlands,” Psychopharmacology Bulletin 43(1): 5–10.
Stitzer, M., Bigelow, G., Lawrence, C., Cohen, J., D’Lugoff, B., and
Hawthorne, J. (1977). “Medication Take-home as a Reinforcer in a Methadone Maintenance Program,” Addictive Behaviors 2(1): 9–14.
The Boston Consulting Group (2003). “The Hidden Epidemic: Finding a Cure for Unfilled Prescriptions and Missed Doses,” Available at https://www.bcg.com/documents/file14265.pdf (accessed January 28, 2016).
Tulsky, J.P., Pilote, L., Hahn, J.A., Zolopa, A.J., Burke, M., Chesney, M., and Moss, A.R. (2000). “Adherence to Isoniazid Prophylaxis in the Homeless: A Randomized Controlled Trial,” Archives of Internal Medicine 160(5): 697–702.
Ward, B.W., Schiller, J.S., and Goodman, R.A. (2014). “Multiple Chronic Conditions among U.S. Adults: A 2012 Update,” Preventing Chronic Disease 11: E62.
Wei, L., Wang, J., Thompson, P., Wong, S., Struthers, A.D., and MacDonald, T.M. (2002). “Adherence to Statin Treatment and Readmission of Patients after Myocardial Infarction: A Six Year Follow Up Study,” Heart 88(3):
229–233.
Wright, C. and Moore, R.D. (1990). “Disulfiram Treatment of Alcoholism,”
The American Journal of Medicine 88(6): 647–655.