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International Journal of Clinical Pharmacy

, Volume 36, Issue 1, pp 128–135 | Cite as

Evidence for compliance with long-term medication: a systematic review of randomised controlled trials

  • Michelle A. KingEmail author
  • Rebecca L. Pryce
Research Article

Abstract

Background Pharmacists play a pivotal role in optimising medication use which often includes actions to maximise compliance with long-term medication. The best evidence to support medication use is derived from randomised controlled trials (RCTs). It is often assumed that 100 % compliance is required to obtain the outcomes identified in the trial. This assumption needs to be examined. Objective To systematically review the reporting of compliance in RCTs of long-term medications. Method RCTs published in the New England Journal of Medicine, Journal of the American Medical Association, Lancet and BMJ in 2012, were reviewed to identify trials of medications for long-term use in adults. These trials were examined to evaluate the reporting of compliance. Main outcome measures The proportion of trials reporting compliance data, the methods used, and the proportion of trials using more than one method to determine compliance. Results Of the 289 RCTs published in 2012, 25 assessed long-term medications in adults. Compliance was reported in 12 (48 %) studies and only 2 (8 %) studies used more than one method to measure compliance. Pill count was the most commonly reported method for measuring compliance, with patient reports and blood levels also being used. Conclusion The reporting of compliance in RCTs is poor and the methodology inconsistent. The methods used overestimate compliance. If compliance in a clinical trial is low, the evidence for the effectiveness and most importantly safety of the medication(s) is questionable. Two or more methods, one of which is standardised, should be used to measure compliance in clinical trials. The requirement to report compliance should be included in publication guidelines.

Keywords

Chronic disease Clinical trials Medication adherence Pharmacoepidemiology Systematic reviews 

Notes

Funding

None.

Conflicts of interest

None.

References

  1. 1.
    Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2095–128.PubMedCrossRefGoogle Scholar
  2. 2.
    Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2163–96.PubMedCrossRefGoogle Scholar
  3. 3.
    Rollason V, Vogt N. Reduction of polypharmacy in the elderly: a systematic review of the role of the pharmacist. Drugs Aging. 2003;20:817–32.PubMedCrossRefGoogle Scholar
  4. 4.
    Milton JC, Hill-Smith I, Jackson SHD. Prescribing for older people. BMJ. 2008;336:606–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Nemes MI, Helena ET, Caraciolo JM, Basso CR. Assessing patient adherence to chronic diseases treatment: differentiating between epidemiological and clinical approaches. Cad Saude Publica. 2009;25(Suppl 3):S392–400.PubMedCrossRefGoogle Scholar
  6. 6.
    Osterberg L, Blaschke T. Adherence to Medication. N Engl J Med. 2005;353:487–97.PubMedCrossRefGoogle Scholar
  7. 7.
    Vrijens B, Vincze G, Kristanto P, Urquhart J, Burnier M. Adherence to prescribed antihypertensive drug treatments: longitudinal study of electronically compiled dosing histories. BMJ. 2008;336:1114–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Pharmaceutical Society of Australia. Standard and guidelines for pharmacists performing clinical interventions 2011. Available from: http://www.psa.org.au/download/practice-guidelines/pharmacists-performing-clinical-interventions-guideline.pdf Accessed 28 Sep 2013.
  9. 9.
    World Health Organisation. Adherence to long-term therapies: evidence for action. Switzerland: World Health Organisation; 2003. Available from: http://www.who.int/chp/knowledge/publications/adherence_report/en/ Accessed 29 June 2013.
  10. 10.
    Soutter BR, Kennedy MC. Patient compliance assessment in drug trials: usage and methods. Aust N Z J Med. 1974;4:360–4.PubMedCrossRefGoogle Scholar
  11. 11.
    Jayaraman S, Rieder MJ, Matsui DM. Compliance assessment in drug trials: has there been improvement in two decades? Can J Clin Pharmacol. 2005;12:e251–3.PubMedGoogle Scholar
  12. 12.
    King MA. Medication care : databases, drug use and outcomes. St Lucia: The University of Queensland; 2003.Google Scholar
  13. 13.
    Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23:1296–310.PubMedCrossRefGoogle Scholar
  14. 14.
    Sav A, King MA, Whitty JA, Kendall E, McMillan SS, Kelly F, et al. Burden of treatment for chronic illness: a concept analysis and review of the literature. Health Expect. 2013.Google Scholar
  15. 15.
    Fogarty L, Roter D, Larson S, Burke J, Gillespie J, Levy R. Patient adherence to HIV medication regimens: a review of published and abstract reports. Patient Educ Couns. 2002;46:93–108.PubMedCrossRefGoogle Scholar
  16. 16.
    Chan AW, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Schulz KF, Altman DG, Moher D, Group C. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c332.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Matsui D. Strategies to measure and improve patient adherence in clinical trials. Pharm Med. 2009;23:289–97.CrossRefGoogle Scholar
  19. 19.
    Smith DL. Patient nonadherence in clinical trials: could there be a link to post marketing patient safety? Drug Inf J. 2012;46:27–34.Google Scholar
  20. 20.
    Garfield S, Clifford S, Eliasson L, Barber N, Willson A. Suitability of measures of self-reported medication adherence for routine clinical use: a systematic review. BMC Med Res Methodol. 2011;11:149.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Cramer JA, Scheyer RD, Mattson RH. Compliance declines between clinic visits. Arch Intern Med. 1990;150:1509–10.PubMedCrossRefGoogle Scholar
  22. 22.
    Felder RA. Testimony of Robin A Felder PhD, Professor of Pathology, Associate Director Clinical Chemistry, The University of Virginia School of Medicine, before the Senate Special Committee on Aging, April 22nd, 2010. Washington DC: 2010.Google Scholar
  23. 23.
    DiMatteo MR, Giordani PJ, Lepper HS, Croghan TW. Patient adherence and medical treatment outcomes: a meta-analysis. Med Care. 2002;40:794–811.PubMedCrossRefGoogle Scholar
  24. 24.
    Simpson SH, Eurich DT, Majumdar SR, Padwal RS, Tsuyuki RT, Varney J, et al. A meta-analysis of the association between adherence to drug therapy and mortality. BMJ. 2006;333:15.PubMedCrossRefGoogle Scholar
  25. 25.
    Steiner JF, Fihn SD, Blair B, Inut TS. Appropriate reductions in compliance among well-controlled hypertensive patients. J Clin Epidemiol. 1991;44:1361–71.PubMedCrossRefGoogle Scholar
  26. 26.
    Brighton TA, Eikelboom JW, Mann K, Mister R, Gallus A, Ockelford P, et al. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012;367:1979–87.PubMedCrossRefGoogle Scholar
  27. 27.
    Comi G, Jeffery D, Kappos L, Montalban X, Boyko A, Rocca MA, et al. Placebo-controlled trial of oral laquinimod for multiple sclerosis. N Engl J Med. 2012;366:1000–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Donnez J, Tatarchuk TF, Bouchard P, Puscasiu L, Zakharenko NF, Ivanova T, et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med. 2012;366:409–20.PubMedCrossRefGoogle Scholar
  29. 29.
    McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366:1770–81.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Morrow DA, Braunwald E, Bonaca MP, Ameriso SF, Dalby AJ, Fish MP, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012;366:1404–13.PubMedCrossRefGoogle Scholar
  31. 31.
    Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012;367:2204–13.PubMedCrossRefGoogle Scholar
  32. 32.
    Roe MT, Armstrong PW, Fox KA, White HD, Prabhakaran D, Goodman SG, et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med. 2012;367:1297–309.PubMedCrossRefGoogle Scholar
  33. 33.
    Sandborn WJ, Ghosh S, Panes J, Vranic I, Su C, Rousell S, et al. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N Engl J Med. 2012;367:616–24.PubMedCrossRefGoogle Scholar
  34. 34.
    Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–97.PubMedCrossRefGoogle Scholar
  35. 35.
    Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366:799–807.PubMedCrossRefGoogle Scholar
  36. 36.
    Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366:1382–92.PubMedCrossRefGoogle Scholar
  37. 37.
    Mega JL, Braunwald E, Wiviott SD, Bassand JP, Bhatt DL, Bode C, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366:9–19.PubMedCrossRefGoogle Scholar
  38. 38.
    Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367:2089–99.PubMedCrossRefGoogle Scholar
  39. 39.
    Thigpen MC, Kebaabetswe PM, Paxton LA, Smith DK, Rose CE, Segolodi TM, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367:423–34.PubMedCrossRefGoogle Scholar
  40. 40.
    Van Damme L, Corneli A, Ahmed K, Agot K, Lombaard J, Kapiga S, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012;367:411–22.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Thadhani R, Appelbaum E, Pritchett Y, Chang Y, Wenger J, Tamez H, et al. Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. JAMA. 2012;307:674–84.PubMedCrossRefGoogle Scholar
  42. 42.
    Fried MW, Navarro VJ, Afdhal N, Belle SH, Wahed AS, Hawke RL, et al. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial. JAMA. 2012;308:274–82.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Lok CE, Moist L, Hemmelgarn BR, Tonelli M, Vazquez MA, Dorval M, et al. Effect of fish oil supplementation on graft patency and cardiovascular events among patients with new synthetic arteriovenous hemodialysis grafts: a randomized controlled trial. JAMA. 2012;307:1809–16.PubMedCrossRefGoogle Scholar
  44. 44.
    Paton NI, Goodall RL, Dunn DT, Franzen S, Collaco-Moraes Y, Gazzard BG, et al. Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: a randomized controlled trial. JAMA. 2012;308:353–61.PubMedCrossRefGoogle Scholar
  45. 45.
    Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, Schvartz M, et al. Multivitamins in the prevention of cardiovascular disease in men: the physicians’ health study II randomized controlled trial. JAMA. 2012;308:1751–60.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Solomon SD, Zile M, Pieske B, Voors A, Shah A, Kraigher-Krainer E, et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet. 2012;380:1387–95.PubMedCrossRefGoogle Scholar
  47. 47.
    van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012;379:1879–86.PubMedCrossRefGoogle Scholar
  48. 48.
    Burant CF, Viswanathan P, Marcinak J, Cao C, Vakilynejad M, Xie B, et al. TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2012;379:1403–11.PubMedCrossRefGoogle Scholar
  49. 49.
    Fleshner NE, Lucia MS, Egerdie B, Aaron L, Eure G, Nandy I, et al. Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial. Lancet. 2012;379:1103–11.PubMedCrossRefGoogle Scholar
  50. 50.
    Gallwitz B, Rosenstock J, Rauch T, Bhattacharya S, Patel S, von Eynatten M, et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet. 2012;380:475–83.PubMedCrossRefGoogle Scholar

Copyright information

© Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2013

Authors and Affiliations

  1. 1.School of Pharmacy, Gold Coast CampusGriffith UniversityGold CoastAustralia

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