Skip to main content
SpringerLink
Log in

Accounting for Noncompliance in Pharmacoeconomic Evaluations

  • Review Article
  • Published:
PharmacoEconomics Aims and scope Submit manuscript

Abstract

Noncompliance with prescribed drug regimens is a widespread phenomenon which results in decreased efficacy and is often associated with increased medical expenditures. Despite this, economic evaluations based on decision-analytic models rarely incorporate noncompliance to allow for the differences in compliance observed between controlled clinical trials and routine clinical practice.

This review examines the issues relating to the measurement of noncompliance, and the clinical and economic consequences of noncompliant drug taking behaviour. In order to fully appreciate the clinical (and therefore the economic) consequences of noncompliance, a detailed understanding of the type of noncompliance, the pharmacokinetic and pharmacodynamic properties of the drug and the pathophysiological processes of the diseases being treated is required. These are described in detail, and a classification of drug-disease combinations according to the potential economic impact of the varying forms of noncompliance is set out.

Issues are raised to highlight the need for improved modelling of the impact of noncompliance, and to this end, recommendations are made for future analyses. The main points are that compliance should be defined clearly, distinguishing between the various forms of noncompliance, that the assumptions relating to the health status of noncompliers should be explicit and robust, and that sensitivity analysis should be applied appropriately to ascertain the impact of noncompliance on the cost-effectiveness of drug therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Fig. 1
Fig. 2
Table III

Similar content being viewed by others

References

  1. Métry J-M, Meyer UA, editors. Drug regimen compliance: issues in clinical trials and patient management. Chichester: John Wiley, 1999

    Google Scholar 

  2. Simon G, Wagner E, Vonkorff M. Cost-effectiveness comparisons using ‘real world’ randomized trials: the case of new antidepressant drugs. J Clin Epidemiol 1995; 48: 363–73

    Article  PubMed  CAS  Google Scholar 

  3. Fayers PM, Hand DJ. Generalisation from phase III clinical trials: survival, quality of life, and health economics. Lancet 1997; 350: 1025–7

    Article  PubMed  CAS  Google Scholar 

  4. Caro JJ, Speckman JL, Salas M, et al. Effect of initial drug choice on persistence with antihypertensive therapy: the importance of actual practice data. CMAJ 1999; 160: 41–6

    PubMed  CAS  Google Scholar 

  5. Andrade SE, Saperia GM, Berger ML, et al. Effectiveness of antihyperlipidemic drug management in clinical practice. Clin Ther 1999; 21: 1973–87

    Article  PubMed  CAS  Google Scholar 

  6. Andrade SE, Walker AM, Gottlieb LK, et al. Discontinuation of antihyperlipidemic drugs — do rates reported in clinical trials reflect rates in primary care settings? N Engl J Med 1995; 332: 1125–31

    Article  PubMed  CAS  Google Scholar 

  7. Revicki DA, Frank L. Pharmacoeconomic evaluations in the real world: effectiveness versus efficacy studies. Pharmacoeconomics 1999; 15: 423–34

    Article  PubMed  CAS  Google Scholar 

  8. Boudes P. Drug compliance in therapeutic trials: a review. Cont Clin Trials 1998; 19: 257–68

    Article  CAS  Google Scholar 

  9. Urquhart J, De Klerk E. Contending paradigms for the interpretation of data on patient compliance with therapeutic drug regimens. Stat Med 1998; 17: 251–67

    Article  PubMed  CAS  Google Scholar 

  10. Beardon PHG, McGilchrist MM, McKendrick AD, et al. Primary non-compliance with prescribed medications in primary care. BMJ 1993; 307: 846–8

    Article  PubMed  CAS  Google Scholar 

  11. Urquhart J, Chevalley C. Impact of unrecognized dosing errors on the cost and effectiveness of pharmaceuticals. Drug Info J 1988; 22: 363–78

    Google Scholar 

  12. Urquhart J. The electronic medication event monitor: lessons for pharmacotherapy. Clin Pharmacokinet 1997; 32: 345–56

    Article  PubMed  CAS  Google Scholar 

  13. Claxton AJ, Cramer JA, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001; 23: 1296–310

    Article  PubMed  CAS  Google Scholar 

  14. Jones JK, Gorkin L, Lian JK, et al. Discontinuation of and changes in treatment after start of new courses of antihypertensive drugs: a study of a United Kingdom population. BMJ 1995; 311: 293–5

    Article  PubMed  CAS  Google Scholar 

  15. Oster G, Borok GM, Menzin J, et al. Cholesterol-reduction intervention study (CRIS): a randomized trial to assess effectiveness and costs in clinical practice. Arch Intern Med 1996; 156: 731–9

    Article  PubMed  CAS  Google Scholar 

  16. Simmons LA, Levis G, Simons J. Apparent discontinuation rates in patients prescribed lipid-lowering drugs. Med J Aust 1996; 164: 208–11

    Google Scholar 

  17. Avorn J, Monette J, Lacour A, et al. Persistence of use of lipidlowering medications: a cross-national study. JAMA 1998; 279: 1458–62

    Article  PubMed  CAS  Google Scholar 

  18. Hiatt JG, Shamsie SG, Schectman G. Discontinuation rates of cholesterol-lowering medications: implications for primary care. Am J Manage Care 1999, 5: 437–44

    CAS  Google Scholar 

  19. Anderson IM, Tomenson BM. Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants: a meta-analysis. BMJ 1995; 310: 1433–8

    Article  PubMed  CAS  Google Scholar 

  20. Paes AHP, Bakker A, Soe-Agnie CJ. Measurement of patient compliance. Pharm World Sci 1998; 20: 73–7

    Article  PubMed  CAS  Google Scholar 

  21. Kastrissios H, Blaschke TF. Medication compliance as a feature in drug development. Annu Rev Pharmacol Toxicol 1997; 37: 451–75

    Article  PubMed  CAS  Google Scholar 

  22. Rudd P, Byyny RL, Zachary V, et al. The natural history of medication compliance in a drug trial: limitations of pill counts. Clin Pharmacol Ther 1989; 46: 169–76

    Article  PubMed  CAS  Google Scholar 

  23. Pullar T, Kumar S, Tundall H, et al. Time to stop counting the tablets? Clin Pharmacol Ther 1989; 46: 163–8

    Article  PubMed  CAS  Google Scholar 

  24. Urquhart J. Ascertaining how much compliance is enough with outpatient antibiotic regimens. Postgrad Med J 1992; 68 Suppl. 3: S49–59

    Google Scholar 

  25. Neumann PJ, Hermann RC, Kuntz KM, et al. Cost-effectiveness of donepezil in the treatment of mild or moderate Alzheimer’s disease. Neurology 1999; 52: 1138–45

    Article  PubMed  CAS  Google Scholar 

  26. Kobelt G, Jonsson L, Mattiasson A. Cost-effectiveness of new treatments for overactive bladder, the example of tolterodine, a new muscarinic agent: a Markov model. Neurourol Urodyn 1998; 17: 599–611

    Article  PubMed  CAS  Google Scholar 

  27. Shiell A, Brown S, Farrell GC. Hepatitis C: an economic evaluation of extended treatment with interferon. Med J Aust 1999; 171: 189–93

    PubMed  CAS  Google Scholar 

  28. Psaty BM, Koepsell TD, Wagner ED, et al. The relative risk of incident coronary heart disease associated with recently stopping the use of β-blockers. JAMA 1990; 263: 1653–7

    Article  PubMed  CAS  Google Scholar 

  29. Vanhove GF, Schapiro JM, Winters MA, et al. Patient compliance and drug failure in protease inhibitor monotherapy. JAMA 1996; 276: 1955–6

    Article  PubMed  CAS  Google Scholar 

  30. Urquhart J. Erratic compliance with prescribed drug regimens: target for drug delivery systems. Clin Pharmacol Ther 2000; 67: 331–4

    Article  PubMed  CAS  Google Scholar 

  31. Young A, Haddad P. Discontinuation symptoms and psychotropic drugs [letter]. Lancet 2000; 355: 1184

    Article  PubMed  CAS  Google Scholar 

  32. 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: 601–15

    Article  PubMed  CAS  Google Scholar 

  33. Urquhart J. Pharmacoeconomic consequences of variable patient compliance with prescribed drug regimens. Pharmacoeconomics 1999; 15: 217–28

    Article  PubMed  CAS  Google Scholar 

  34. Lafata JE, Martin SA, Kaatz S, et al. The cost-effectiveness of different management strategies for patients on chronic warfarin therapy. J Gen Intern Med 2000; 15: 31–7

    Article  PubMed  CAS  Google Scholar 

  35. Drummond MF, editor. Methods for the economic evaluation of health care programmes. 2nd ed. Oxford: Oxford University Press, 1997

    Google Scholar 

  36. Buxton MJ, Drummond MF, Van Hout BA, et al. Modelling in economic evaluation: an unavoidable fact of life. Health Econ 1997; 6: 217–27

    Article  PubMed  CAS  Google Scholar 

  37. Rosner AJ, Grima DT, Torrance GW, et al. Cost effectiveness of multi-therapy treatment strategies in the prevention of vertebral fractures in postmenopausal women with osteoporosis. Pharmacoeconomics 1998; 14: 559–73

    Article  PubMed  CAS  Google Scholar 

  38. Hughes D, Manns B. Patient compliance with drug therapy for diabetic nephropathy [letter]. CMAJ 2000; 162: 1553

    PubMed  CAS  Google Scholar 

  39. Harter JG, Peck CC. Chronobiology: suggestions for integrating it into drug development. Ann NY Acad Sci 1991; 618: 563–71

    Article  PubMed  CAS  Google Scholar 

  40. Rubio A, Cox C, Weintraub M. Prediction of diltiazem plasma concentration curves from limited measurements using compliance data. Clin Pharmacol 1992; 22: 238–46

    Article  CAS  Google Scholar 

  41. Wang W, Husam F, Chow S-C. The impact of patient compliance on drug concentration profile in multiple doses. Stat Med 1996; 15: 659–69

    Article  PubMed  CAS  Google Scholar 

  42. Girard P, Blaschke TF, Kastrissios H, et al. A Markov mixed effect regression model for drug compliance. Stat Med 1998; 17: 2313–33

    Article  PubMed  CAS  Google Scholar 

  43. Meibohm B, Derendorf H. Basic concepts of pharmacokinetic/pharmacodynamic (PK/PD) modelling. Int J Clin Pharmacol Ther 1997; 35: 401–13

    PubMed  CAS  Google Scholar 

  44. Gieschke R, Reigner BG, Steimer J-L. Exploring clinical study design by computer simulation based on pharmacokinetic/pharmacodynamic modelling. Int J Clin Pharmacol Ther 1997; 35: 469–74

    PubMed  CAS  Google Scholar 

  45. Holford NH, Kimko HC, Monteleone JP, et al. Clinical trial simulations. Ann Rev Pharmacol Toxicol 2000; 40: 209–34

    Article  CAS  Google Scholar 

  46. Hughes DA, Bagust A, Haycox A, et al. The influence of noncompliance on the effectiveness and cost-effectiveness of drug therapies [abstract]. Value Health 2000; 3: 373

    Article  Google Scholar 

  47. Wahl LM, Nowak MA. Adherence and drug resistance: predictions for therapy outcome. Proc R Soc Lond B 2000; 267: 835–43

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Supported by a National Health Service Executive North West Regional Office, R & D Post-doctoral fellowship award.

Author information

Authors and Affiliations

  1. Prescribing Research Group, Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, L69 3GE, UK

    Dyfrig A. Hughes, Adrian Bagust, Alan Haycox & Tom Walley

Authors
  1. Dyfrig A. Hughes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adrian Bagust
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alan Haycox
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tom Walley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dyfrig A. Hughes.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hughes, D.A., Bagust, A., Haycox, A. et al. Accounting for Noncompliance in Pharmacoeconomic Evaluations. Pharmacoeconomics 19, 1185–1197 (2001). https://doi.org/10.2165/00019053-200119120-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00019053-200119120-00001

Keywords

Search

Navigation