Participant Adherence

  • Lawrence M. Friedman
  • Curt D. Furberg
  • David L. DeMets
  • David M. Reboussin
  • Christopher B. Granger


The terms compliance and adherence are often used interchangeably. In 1979, Haynes et al., defined compliance as “the extent to which a person’s behavior (in terms of taking medications, following diets or executing lifestyle changes) coincides with medical or health advice” [1]. More recently, an international consensus statement crafted by the World Health Organization and the International Society of Pharmacoeconomics and Outcomes Research defined medication adherence as “the extent to which a patient acts in accordance with the prescribed interval and dose of a dosing regime” [2]. Patient adherence is also recently reviewed in additional articles [3–5]. The term adherence implies active participant involvement in the decision to take a medication, use a device or engage in a behavior change, and is the term used in this book. In this chapter, we primarily refer to drug adherence but the concepts apply generally. In a drug trial, adherence typically refers to ingestion of predetermined amount of drug such as 80% of the protocol dose. This dose will depend on the nature and half-life of the drug being evaluated. Persistence is a related term that refers to remaining on a medical treatment for a specified period of time, regardless of the proportion of the doses taken. Distinguishing adherence vs. persistence is important since the metrics are different as well as the implications for trial interpretation [6, 7].


Medication Adherence Pill Count Optimal Medical Therapy Schedule Visit Drug Adherence 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Haynes RB, Taylor DW, Sackett DL (eds.). Compliance in Health Care. Baltimore: Johns Hopkins University Press, 1979.Google Scholar
  2. 2.
    Cramer JA, Roy A, Burrell A, et al. Medication compliance and persistence: terminology and definitions. Value Health 2008;11:44-47.CrossRefGoogle Scholar
  3. 3.
    Vrijens B, De Geest S, Hughes DA, et al. A new taxonomy for describing and defining adherence to medications. Br J Clin Pharmacol 2012;73:691-705.Google Scholar
  4. 4.
    Zeber JE, Manias E, Williams AF, et al. A systematic literature review of psychosocial and behavioral factors associated with initial medication adherence: a report of the ISPOR medication adherence & persistence special interest group. Value Health 2013;16:891-900.CrossRefGoogle Scholar
  5. 5.
    Raebel MA, Schmittdiel J, Karter AJ, et al. Standardizing terminology and definitions of medication adherence and persistence in research employing electronic databases. Med Care 2013;51:S11-S21.CrossRefGoogle Scholar
  6. 6.
    Eapen Z, Mi X, Qualls LG, et al. Adherence and persistence in the use of warfarin after hospital discharge among patients with heart failure and atrial fibrillation. J Card Fail 2014;20:23-30.CrossRefGoogle Scholar
  7. 7.
    Granger BB, Rusincovitch SA, Avery S, et al. Missing signposts on the roadmap to quality: a call to improve medication adherence indicators in data collection for population research. Front Pharmacol 2013;4:139.CrossRefGoogle Scholar
  8. 8.
    Peterson AM, Takiya L, Finley R. Meta-analysis of trials of interventions to improve medication adherence. Am J Health-Syst Pharm 2003;60:657-665.Google Scholar
  9. 9.
    Cutler DM, Everett W. Thinking outside the pillbox—medication adherence as a priority for health care reform. N Engl J Med 2010;362:1553-1555.CrossRefGoogle Scholar
  10. 10.
    Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005;353:487-497.CrossRefGoogle Scholar
  11. 11.
    Riekert KA, Ockene JK, Pbert L (eds.). The Handbook of Health Behavior Change (4th edition). New York: Springer Publishing Company, 2014.Google Scholar
  12. 12.
    Boden WE, O’Rourke RA, Teo KK, et al for the COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007;356:1503-1516.CrossRefGoogle Scholar
  13. 13.
    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, randomized, controlled clinical trial. Lancet 2005;366:2005-2011.CrossRefGoogle Scholar
  14. 14.
    DiMatteo MR. Variations in patients’ adherence to medical recommendations. A quantitative review of 50 years of research. Med Care 2004;42:200-209.CrossRefGoogle Scholar
  15. 15.
    Härkäpää K, Järvikoski A, Mellin G, Hurri H. A controlled study of the outcome of inpatient and outpatient treatment of low back pain. Part I. Pain, disability, compliance, and reported treatment benefits three months after treatment. Scand J Rehabil Med 1989;21:81-89.Google Scholar
  16. 16.
    McLean N, Griffin S, Toney K, Hardeman W. Family involvement in weight control, weight maintenance and weight-loss interventions: a systematic review of randomised trials. Intern J Obesity 2003;27:987-1005.CrossRefGoogle Scholar
  17. 17.
    Voils CI, Yancy Jr WS, Kovac S, et al. Study protocol: Couples Partnering for Lipid Enhancing Strategies (CouPLES)—a randomized, controlled trial. Trials 2009;10:10-19.CrossRefGoogle Scholar
  18. 18.
    Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. N Engl J Med 2001;344:3-10.CrossRefGoogle Scholar
  19. 19.
    Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001;23:1296-1310.CrossRefGoogle Scholar
  20. 20.
    Probstfield JL. The clinical trial prerandomization compliance (adherence) screen. In Cramer JA, Spilker B (eds.). Patient Compliance in Medical Practice and Clinical Trials. New York: Raven Press, 1991.Google Scholar
  21. 21.
    Berger VW, Rezvani A, Makarewicz VA. Direct effect on validity of response run-in selection in clinical trials. Control Clin Trials 2003;24;156-166.CrossRefGoogle Scholar
  22. 22.
    Lang JM, Buring JE, Rosner B, et al. Estimating the effect of the run-in on the power of the Physicians' Health Study. Stat Med 1991;10:1585-1593.CrossRefGoogle Scholar
  23. 23.
    McMurray JJV, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993-1004.CrossRefGoogle Scholar
  24. 24.
    Lee S, Walker JR, Jakul L, Sexton K. Does elimination of placebo responders in a placebo run-in increase the treatment effect in randomized clinical trials? A meta-analytic evaluation. Depress Anxiety 2004;19:10-19.CrossRefGoogle Scholar
  25. 25.
    Kingry C, Bastien A, Booth G, et al. for the ACCORD Study Group. Recruitment strategies in the Action to Control Cardiovascular Risk of Diabetes (ACCORD) Trial. Am J Cardiol 2007;99[suppl]:68i-79i.Google Scholar
  26. 26.
    Williams SL, Haskard-Zolnierik KB, DiMatteo MR. Psychosocial predictors of behavioral change. In Riekert KA, Ockene JK, Pbert L (eds.). The Handbook of Health Behavior Change (4th edition). New York: Springer Publishing Company, 2014, pp. 69-86.Google Scholar
  27. 27.
    Youmans SL, Schillinger D. Functional health literacy and medication use: the pharmacist’s role. Ann Pharmacother 2003;37:1726-1729.CrossRefGoogle Scholar
  28. 28.
    Wolf MS, Davis TC, Osborn CY, et al. Literacy, self-efficacy, and HIV medication adherence. Pat Educ Counsel 2007;65:253-260.CrossRefGoogle Scholar
  29. 29.
    Daumit GL, Dickerson FB, Wang NY, et al. A behavioral weight-loss intervention in persons with serious mental illness. N Engl J Med 2013;368:1594-1602.CrossRefGoogle Scholar
  30. 30.
    Kimmel SE, Troxel AB, Loewenstein G, et al. Randomized trial of lottery-based incentives to improve warfarin adherence. Am Heart J 2012;164:268-274.CrossRefGoogle Scholar
  31. 31.
    Ryan R, Santesso N, Lowe D. et al. Interventions to improve safe and effective medicines use by consumers: an overview of systematic reviews. Cochrane Database Syst Rev 2014;4:CD007768.Google Scholar
  32. 32.
    DeFulio A, Silverman K. The use of incentives to reinforce medication adherence. Prev Med 2012;55:S86-S94.CrossRefGoogle Scholar
  33. 33.
    Hiligsmann M, Salas M, Hughes DA, et al. Interventions to improve osteoporosis medication adherence and persistence: a systematic review and literature appraisal by the ISPOR medication adherence & persistence special interest group. Osteoporos Int 2013;24:2907-2918.CrossRefGoogle Scholar
  34. 34.
    Scheurer D, Choudhry N, Swanton KA, et al. Association between different types of social support and medication adherence. Am J Manag Care 2012;18:e461-e467.Google Scholar
  35. 35.
    Barnes K. Patients provide insight into trial participation., July 4, 2007.
  36. 36.
    Kessels RPC. Patients’ memory for medical information. J R Soc Med 2003;96:219-222.CrossRefGoogle Scholar
  37. 37.
    Anderson JL, Dodman S, Kopelman M, et al. Patient information recall in a rheumatology clinic. Rheumatology 1979;18:18-22.CrossRefGoogle Scholar
  38. 38.
    Tamur-Lis W. Teach-back for quality education and patient safety. Urol Nurs 2013;33:267-271.Google Scholar
  39. 39.
    White M, Garbez R, Carroll M, et al. Is “teach-back” associated with knowledge retention and hospital readmission in hospitalized heart failure patients? J Cardiovasc Nurs 2013;28:137-146.CrossRefGoogle Scholar
  40. 40.
    Xie L, Frech-Tamas F, Marrett E, Baser O. A medication adherence and persistence comparison of hypertensive patients treated with single-, double- and triple-pill combination therapy. Curr Med Res Opin 2014;29:1-8.Google Scholar
  41. 41.
    Demonceau J, Ruppar T, Kristanto P, et al. Identification and assessment of adherence-enhancing interventions in studies assessing medication adherence through electronically compiled drug dosing histories: a systematic literature review and meta-analysis. Drugs 2013;73:545-562.CrossRefGoogle Scholar
  42. 42.
    Zullig LL, Peterson ED, Bosworth HB. Ingredients of successful interventions to improve medication adherence. JAMA 2013;310:2611-2612.CrossRefGoogle Scholar
  43. 43.
    Dexheimer JW, Sanders DL, Rosenbloom ST, et al. Prompting clinicians: A systematic review of prevention care reminders. AMIA Annu Symp Proc. 2005; 2005;938.Google Scholar
  44. 44.
    Hasvold PE, Wootton R. Use of telephone and SMS reminders to improve attendance at hospital appointments: a systematic review. J Telemed Telecare 2011;17:358-364.CrossRefGoogle Scholar
  45. 45.
    Gurol-Urganci I, de Jongh T, Vodopivec-Jamsek V, et al. Mobile phone messaging reminders for attendance at healthcare appointments. Cochrane Database of Systematic Reviews 2013, Issue 12Google Scholar
  46. 46.
    Vervloet M, Linn AJ, vanWeert, JCM, et al. The effectiveness of interventions using electronic reminders to improve adherence to chronic medication: a systematic review of the literature. J Am Med Inform Assoc, 2012; 19:696-704.CrossRefGoogle Scholar
  47. 47.
    Granger BB, Bosworth H. Medication adherence: emerging use of technology. Curr Opin Cardiol. 2011; 26:279-287.CrossRefGoogle Scholar
  48. 48.
    Shea SC. Improving medication adherence: How to talk with patients about their medications. Philadelphia: Lippincott, Williams & Wilkins, 2006.Google Scholar
  49. 49.
    Morisky DE, Ang A, Krousel-Wood M, Ward HJ. Predictive validity of a medication adherence measure in an outpatient setting. J Clin Hypertens 2008;10:348-354.CrossRefGoogle Scholar
  50. 50.
    Probstfield JL, Russell ML, Henske JC, et al. Successful program for recovery of dropouts to a clinical trial. Am J Med 1986;80:777-784.CrossRefGoogle Scholar
  51. 51.
    Gossec L, Tubach F, Dougados M, Ravaud P. Reporting of adherence to medication in recent randomized controlled trials of 6 chronic diseases: A systematic literature review. Am J Med Sci 2007;334:248-254.CrossRefGoogle Scholar
  52. 52.
    Vrijens B, Rousset 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;45:461-467.CrossRefGoogle Scholar
  53. 53.
    Vrijens B, Vincze G, Kristanto P, et al. Adherence to prescribed antihypertensive drug treatments: longitudinal study of electronically compiled dosing histories. Br Med J 2008;336:1114-1117.CrossRefGoogle Scholar
  54. 54.
  55. 55.
    Hayman LL, Mruk MM. Chronic disease management interventions: cardiovascular disease. In Riekert KA, Ockene JK, Pbert L (eds). The Handbook of Health Behavior Change (4th edition). New York, Springer Publishing Company, 2014, pp 273-289.Google Scholar
  56. 56.
    Hood KK, Raymond JK, Harris MA. Diabetes management behaviors: The key to optimal health and quality of life outcomes. In Riekert KA, Ockene JK, Pbert L (eds). The Handbook of Health Behavior Change (4th edition). New York, Springer Publishing Company, 2014, pp 291-308.Google Scholar
  57. 57.
    Welkom JS, Riekert KA, Eakin, MN, et al. Behavioral management of chronic respiratory diseases: examples from asthma and chronic obstructive pulmonary disease. In Riekert KA, Ockene JK, Pbert L (eds). The Handbook of Health Behavior Change (4th edition). New York, Springer Publishing Company, 2014, pp 309-329.Google Scholar
  58. 58.
    Rhodes SD, Wilkin AM, Abraham C, Bachmann LH. Chronic infectious disease management interventions. In Riekert KA, Ockene JK, Pbert L (eds). The Handbook of Health Behavior Change (4th edition). New York, Springer Publishing Company, 2014, pp 331-345.Google Scholar
  59. 59.
    Peterman AH, Victorson D, Cella D. Adherence to treatment and lifestyle changes among people with cancer. In Riekert KA, Ockene JK, Pbert L (eds). The Handbook of Health Behavior Change (4th edition). New York, Springer Publishing Company, 2014, pp 347-362.Google Scholar
  60. 60.
    Burke LE, Turk MW. Obesity. In Riekert KA, Ockene JK, Pbert L (eds). The Handbook of Health Behavior Change (4th edition). New York, Springer Publishing Company, 2014, pp 363-378.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Lawrence M. Friedman
    • 1
  • Curt D. Furberg
    • 2
  • David L. DeMets
    • 3
  • David M. Reboussin
    • 4
  • Christopher B. Granger
    • 5
  1. 1.North BethesdaUSA
  2. 2.Division of Public Health SciencesWake Forest School of MedicineWinston-SalemUSA
  3. 3.Department Biostatistics and Medical InformaticsUniversity of WisconsinMadisonUSA
  4. 4.Department of BiostatisticsWake Forest School of MedicineWinston-SalemUSA
  5. 5.Department of MedicineDuke UniversityDurhamUSA

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