Abstract
Non-compliance with prescribed regimens poses a significant problem in clinical therapeutics — patients who do not take their medications according to the labelling instructions are at higher risk of treatment failure, and this may have adverse effects on health outcome and healthcare costs. There is increasing evidence on strategies aimed at improving compliance, but most studies do not implement an unbiased technique for measuring compliance. Patients and clinicians alike are notoriously unreliable in assessing compliance; the use of electronic compliance-monitoring devices (ECMDs) is one of the most robust ways to identify non-compliance and assess the effectiveness of interventions aimed at promoting compliance. ECMDs may also form a part of the intervention, by allowing the health professional to provide feedback to the patient on his/her dosing history. This approach has been referred to as a ‘measurement-guided medication management (MGMM) programme’.
This article reviews the evidence on the effectiveness of MGMM programmes based on ECMDs, and sets out a framework for assessing their economic value. Existing studies focus primarily on the impact of MGMM programmes on compliance. However, to generalise to other settings, including routine practice, further evidence is required on their clinical and cost effectiveness. Specifically, more studies are required to assess whether the observed improvements in compliance translate to improvements in health outcomes, and whether these may be achieved in a cost-effective manner.
Similar content being viewed by others
Notes
The ROC is a graphical plot of the sensitivity versus (1 — specificity) for a binary classifier system (responder/nonresponder) as its discrimination threshold (percentage compliance) is varied.
References
Why treatments fail. Drug Ther Bull 1998; 36 (6): 47-8
Simpson SH, Eurich DT, Majumdar SR, et al. A meta-analysis of the association between adherence to drug therapy and mortality. BMJ 2006; 333 (7557): 15
Biondi-Zoccai GG, Lotrionte M, Agostoni P, et al. A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Eur Heart J 2006; 27 (22): 2667–2674
Cramer JA, Glassman M, Rienzi V. The relationship between poor medication compliance and seizures. Epilepsy Behav 2002; 3: 338–342
Burnier M, Schneider MP, Chiolero A, et al. Electronic compliance monitoring in resistant hypertension: the basis for rational therapeutic decisions. J Hypertens 2001; 19: 335–341
Urquhart J. The odds of the three nons when an aptly prescribed medicine isn’t working: non-compliance, non-absorption, non-response. Br J Clin Pharmacol 2002; 54: 212–220
Wright EC. Non-compliance: or how many aunts has Matilda? Lancet 1993; 342 (8876): 909–913
Farmer KC. Methods for measuring and monitoring medication regimen adherence in clinical trials and clinical practice. Clin Ther 1999; 21 (6): 1074–1090
Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005; 353 (5): 487–497
Urquhart J. The electronic medication event monitor: lessons for pharmacotherapy. Clin Pharmacokinet 1997; 32: 345–356
Garber MC, Nau DP, Erickson SR, et al. The concordance of self-report with other measures of medication adherence: a summary of the literature. Med Care 2004; 42 (7): 649–652
Pullar T, Kumar S, Tindall H, et al. Time to stop counting the tablets? Clin Pharmacol Ther 1989; 46 (2): 163–168
Cramer JA, Mattson RH, Prevey ML, et al. How often is medication taken as prescribed? A novel assessment technique [published erratum appears in JAMA 1989; 262 (11): 1472]. JAMA 1989; 261 (22): 3273–3277
Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001; 23: 1296–1310
Vrijens B, Tousset E, Rode R, et al. Successful projection of the time course of drug concentration in plasma during a 1-year period from electronically compiled dosing-time data used as input to individually parameterized pharmacokinetic models. J Clin Pharmacol 2005; 45 (4): 461–467
Liu H, Golin CE, Miller LG, et al. A comparison study of multiple measures of adherence to HIV protease inhibitors. Ann Intern Med 2001; 134: 968–977
Namkoong K, Farren CK, O’Connor PG, et al. Measurement of compliance with naltrexone in the treatment of alcohol dependence: research and clinical implications. J Clin Psychiatry 1999; 60: 449–453
Bova CA, Fennie KP, Knafl GJ, et al. Use of electronic monitoring devices to measure antiretroviral adherence: practical considerations. AIDS Behav 2005; 9 (1): 103–110
Wendel CS, Mohler MJ, Kroesen K, et al. Barriers to use of electronic adherence monitoring in an HIV clinic. Ann Pharmacother 2001; 35: 1010–1015
Cramer JA, Ouellette VL, Mattson RH. The effect of microelectronic observation on compliance. Epilepsia 1990; 31: 617–618
Matsui D, Hermann C, Klein J, et al. Critical comparison of novel and existing methods of compliance assessment during a clinical trial of an oral iron chelator. J Clin Pharmacol 1994; 34 (9): 944–949
Rosen MI, Rigsby MO, Salahi JT, et al. Electronic monitoring and counseling to improve medication adherence. Behav Res Ther 2004; 42 (4): 409–422
Rosen MI, Ryan C, Rigsby MO. Motivational enhancement and MEMS review to improve medication adherence. Behaviour change 2002; 19 (4): 183–190
Schmitz JM, Sayre SL, Stotts AL, et al. Medication compliance during a smoking cessation clinical trial: a brief intervention using MEMS feedback. J Behav Med 2005; 28 (2): 139–147
Mooney ME, Sayre SL, Hokanson PS, et al. Adding MEMS feedback to behavioral smoking cessation therapy increases compliance with bupropion: a replication and extension study. Addict Behav 2007; 32 (4): 875–880
Cramer J, Rosenheck R, Kirk G, et al. Medication compliance feedback and monitoring in a clinical trial: predictors and outcomes. Value Health 2003; 6 (5): 566–573
Vrijens B, Belmans A, Matthys K, et al. Effect of intervention through a pharmaceutical care program on patient adherence with prescribed once-daily atorvastatin. Pharmacoepidemiol Drug Saf 2006; 15 (2): 115–121
Bouvy ML, Heerdink ER, Urquhart J, et al. Effect of a pharmacistled intervention on diuretic compliance in heart failure patients: a randomized controlled study. J Card Fail 2003; 9 (5): 404–411
Matsuyama JR, Mason BJ, Jue SG. Pharmacists’ interventions using an electronic medication-event monitoring device’s adherence data versus pill counts. Ann Pharmacother 1993; 27 (7-8): 851–855
Cramer JA, Rosenheck R. Enhancing medication compliance for people with serious mental illness. J Nerv Ment Dis 1999; 187 (1): 53–55
Elixhauser A, Eisen SA, Romeis JC, et al. The effects of monitoring and feedback on compliance. Med Care 1990; 28 (10): 882–893
Nides MA, Tashkin DP, Simmons MS, et al. Improving inhaler adherence in a clinical trial through the use of the nebulizer chronolog. Chest 1993; 104 (2): 501–507
Smith SR, Rublein JC, Marcus C, et al. A medication self-management program to improve adherence to HIV therapy regimens. Patient Educ Couns 2003; 50 (2): 187–199
Rigsby MO, Rosen MI, Beauvais JE, et al. Cue-dose training with monetary reinforcement: pilot study of an antiretroviral adherence intervention. J Gen Intern Med 2000; 15 (12): 841–847
de Bruin M, Hospers HJ, van den Borne HW, et al. Theory- and evidence-based intervention to improve adherence to antire-troviral therapy among HIV-infected patients in the Netherlands: a pilot study. AIDS Patient Care STDS 2005; 19 (6): 384–394
Ickovics JR, Cameron A, Zackin R, et al. Consequences and determinants of adherence to antiretroviral medication: results from Adult AIDS Clinical Trials Group protocol 370. Antivir Ther 2002; 7: 185–193
Chesney M. Adherence to HAART regimens. AIDS Patient Care STDS 2003; 17: 169–177
Urquhart J. Pharmacodynamics of variable patient compliance: implications for pharmaceutical value. Adv Drug Deliv Rev 1998; 33: 207–219
Mousa SA, Forsythe MS, Bozarth JM, et al. Effect of single oral dose of aspirin on human platelet functions and plasma plasminogen activator inhibitor-1. Cardiology 1993; 83: 367–373
Leenen FH, Fourney A, Notman G, et al. Persistence of anti-hypertensive effect after. Br J Clin Pharmacol 1996; 41: 83–88
Hughes DA, Walley T. Predicting’ real world’ effectiveness by integrating adherence with pharmacodynamic modeling. Clin Pharmacol Ther 2003; 74: 1–8
McNabb J, Ross JW, Abriola K, et al. Adherence to highly active antiretroviral therapy predicts virologic outcome at an innercity human immunodeficiency virus clinic. Clin Infec Dis 2001; 33: 700–705
Arnsten JH, Demas PA, Farzadegan H, et al. Antiretroviral therapy adherence and viral suppression in HIV-infected drug users: comparison of self-report and electronic monitoring. Clin Infec Dis 2001; 33: 1417–1423
Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000; 133: 21–30
Bangsberg DR, Hecht FM, Charlebois ED, et al. Adherence to protease inhibitors, HIV-1 viral load, and development of drug resistance in an indigent population. AIDS 2000; 14: 357–366
Howard AA, Arnsten JH, Lo Y, et al. A prospective study of adherence and viral load in a large multi-center cohort of HIV-infected women. AIDS 2002; 16: 2175–2182
Nichol MB, Venturini F, Sung JC. A critical evaluation of the methodology of the literature on medication compliance. Ann Pharmacother 1999; 33: 531–540
DiMatteo MR, Giordani PJ, Lepper HS, et al. Patient adherence and medical treatment outcomes: a meta-analysis. Med Care 2002; 40 (9): 794–811
Haynes RB, Yao X, Degani A, et al. Interventions to enhance medication adherence. Cochrane Database Syst Rev 2002; (2): CD000011
Hughes D. Less is more: medicines that require less frequent administration improve adherence, but are they better? Pharmacoeconomics 2006; 24 (3): 211–213
Elliott RA, Barber N, Horne R. Cost-effectiveness of adherence-enhancing interventions: a quality assessment of the evidence. Ann Pharmacother 2005; 39: 508–515
Hughes DA, Cowell W, Koncz T, et al. Methods for integrating medication compliance and persistence in pharmacoeconomic evaluations. Value Health. Epub 2007 May 22
Wetzels GE, Nelemans P, Schouten JS, et al. Facts and fiction of poor compliance as a cause of inadequate blood pressure control: a systematic review. J Hypertens 2004; 22: 1849–1855
Granger BB, Swedberg K, Ekman I, et al. Adherence to candesartan and placebo and outcomes in chronic heart failure in the CHARM programme: double-blind, randomised, controlled clinical trial. Lancet 2005; 366: 2005–2011
Hughes DA, Bagust A, Haycox A, et al. The impact of non-compliance on the cost-effectiveness of pharmaceuticals: a review of the literature. Health Econ 2001; 10 (7): 601–615
Ledergerber B, Egger M, Opravil M, et al. Clinical progression and virological failure on highly active anti-retroviral therapy in HIV-1 patients: a prospective cohort study. Lancet 1999; 353: 863–868
Wit FW, van Leeuwen R, Weverling GJ, et al. Outcome and predictors of failure of highly active antiretroviral therapy: one-year follow-up of a cohort of human immunodeficiency virus type 1-infected persons. J Infect Dis 1999; 179: 790–798
Mills EJ, Nachega JB, Bangsberg DR, et al. Adherence to HAART: a systematic review of developed and developing nation patient-reported barriers and facilitators. PLoS Med 2006; 3 (11): e438
Zhou X-H, Obuchowski NA, McClish DK, editors. Statistical methods in diagnostic medicine. New York: John Wiley & Sons, Inc., 2002
Negredo E, Bonjoch A, Clotet B. Benefits and concerns of simplification strategies in HIV-infected patients. J Antimicrob Chemother 2006; 58 (2): 235–242
Tashima KT, Mitty JA. Once-daily therapies for the treatment of HIV infection. Curr HIV/AIDS Rep 2006; 3 (2): 86–92
Rueda S, Park-Wyllie LY, Bayoumi AM, et al. Patient support and education for promoting adherence to highly active antiretroviral therapy for HIV/AIDS. Cochrane Database Syst Rev 2006; 3: CD001442
Simoni JM, Pearson CR, Pantalone DW, et al. Efficacy of interventions in improving highly active antiretroviral therapy adherence and HIV-1 RNA viral load: a meta-analytic review of randomized controlled trials. J Acquir Immune Defic Syndr 2006; 43 Suppl. 1: S23–S35
Munakata J, Benner JS, Becker S, et al. Clinical and economic outcomes of nonadherence to highly active antiretroviral therapy in patients with human immunodeficiency virus. Med Care 2006; 44 (10): 893–899
Goldie SJ, Paltiel AD, Weinstein MC, et al. Projecting the cost-effectiveness of adherence interventions in persons with human immunodeficiency virus infection. Am J Med 2003; 115 (8): 632–641
Acknowledgements
The author has no conflicts of interest directly relevant to the contents of this paper. No sources of funding were used to assist in the preparation of this work.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hughes, D. When Drugs Don’t Work. Pharmacoeconomics 25, 621–635 (2007). https://doi.org/10.2165/00019053-200725080-00001
Published:
Issue Date:
DOI: https://doi.org/10.2165/00019053-200725080-00001