Original Research1 April 2014
A Cohort Study
    Author, Article, and Disclosure Information



    Primary nonadherence is probably an important contributor to suboptimal disease management, but methodological challenges have limited investigation of it.


    To estimate the incidence of primary nonadherence in primary care and the drug, patient, and physician characteristics that are associated with nonadherence.


    A prospective cohort of patients and all their incident prescriptions from primary care electronic health records between 2006 and 2009 linked to provincial drug insurer data on all drugs dispensed from community-based pharmacies were assembled.


    Quebec, Canada.


    15 961 patients in a primary care network of 131 physicians.


    Primary nonadherence was defined as not filling an incident prescription within 9 months. Multivariate alternating logistic regression was used to estimate predictors of nonadherence and account for patient and physician clustering.


    Overall, 31.3% of the 37 506 incident prescriptions written for the 15 961 patients were not filled. Drugs in the upper quartile of cost were least likely to be filled (odds ratio [OR], 1.11 [95% CI, 1.07 to 1.17]), as were skin agents, gastrointestinal drugs, and autonomic drugs, compared with anti-infectives. Reduced odds of nonadherence were associated with increasing patient age (OR per 10 years, 0.89 [CI, 0.85 to 0.92]), elimination of prescription copayments for low-income groups (OR, 0.37 [CI, 0.32 to 0.41]), and a greater proportion of all physician visits with the prescribing physician (OR per 0.5 increase, 0.77 [CI, 0.70 to 0.85]).


    Patients' rationale for choosing not to fill their prescriptions could not be measured.


    Primary nonadherence is common and may be reduced by lower drug costs and copayments, as well as increased follow-up care with prescribing physicians for patients with chronic conditions.

    Primary Funding Source:

    Canadian Institutes of Health Research.


    • 1. Halpin HAMorales-Suárez-Varela MMMartin-Moreno JMChronic disease prevention and the new public health. Public Health Rev2010;32:120-54. CrossrefGoogle Scholar
    • 2. Daar ASSinger PAPersad DLPramming SKMatthews DRBeaglehole Ret alGrand challenges in chronic non-communicable diseases. Nature2007;450:494-6. [PMID: 18033288] CrossrefMedlineGoogle Scholar
    • 3. van der Linden CMJansen PAvan Geerenstein EVvan Marum RJGrouls RJEgberts TCet alReasons for discontinuation of medication during hospitalization and documentation thereof: a descriptive study of 400 geriatric and internal medicine patients [Letter]. Arch Intern Med2010;170:1085-7. [PMID: 20585080] MedlineGoogle Scholar
    • 4. Tunstall-Pedoe H. Preventing Chronic Diseases. A Vital Investment. WHO Global Report. Geneva: World Health Organization; 2005. Accessed at www.who.int/chp/chronic_disease_report/en on 31 January 2014. Google Scholar
    • 5. Ho PMBryson CLRumsfeld JSMedication adherence: its importance in cardiovascular outcomes. Circulation2009;119:3028-35. [PMID: 19528344] CrossrefMedlineGoogle Scholar
    • 6. Yang YThumula VPace PFBanahan BFWilkin NELobb WBMedication nonadherence and the risks of hospitalization, emergency department visits, and death among Medicare Part D enrollees with diabetes. Drug Benefit Trends2009;21:330-8. Google Scholar
    • 7. Halm EAMora PLeventhal HNo symptoms, no asthma: the acute episodic disease belief is associated with poor self-management among inner-city adults with persistent asthma. Chest2006;129:573-80. [PMID: 16537854] CrossrefMedlineGoogle Scholar
    • 8. Solomon MDMajumdar SRPrimary non-adherence of medications: lifting the veil on prescription-filling behaviors [Editorial]. J Gen Intern Med2010;25:280-1. [PMID: 20195783] CrossrefMedlineGoogle Scholar
    • 9. Jackevicius CAMamdani MTu JVAdherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA2002;288:462-7. [PMID: 12132976] CrossrefMedlineGoogle Scholar
    • 10. Storm AAndersen SEBenfeldt ESerup JOne in 3 prescriptions are never redeemed: primary nonadherence in an outpatient clinic. J Am Acad Dermatol2008;59:27-33. [PMID: 18467003] CrossrefMedlineGoogle Scholar
    • 11. Shah NRHirsch AGZacker CWood GCSchoenthaler AOgedegbe Get alPredictors of first-fill adherence for patients with hypertension. Am J Hypertens2009;22:392-6. [PMID: 19180061] CrossrefMedlineGoogle Scholar
    • 12. Ko DTChiu MGuo HAustin PCMarquis JFTu JVPatterns of use of thienopyridine therapy after percutaneous coronary interventions with drug-eluting stents and bare-metal stents. Am Heart J2009;158:592-598.e1. [PMID: 19781419] CrossrefMedlineGoogle Scholar
    • 13. Fischer MAStedman MRLii JVogeli CShrank WHBrookhart MAet alPrimary medication non-adherence: analysis of 195,930 electronic prescriptions. J Gen Intern Med2010;25:284-90. [PMID: 20131023] CrossrefMedlineGoogle Scholar
    • 14. Fischer MAChoudhry NKBrill GAvorn JSchneeweiss SHutchins Det alTrouble getting started: predictors of primary medication nonadherence. Am J Med2011;124:1081.e9-22. [PMID: 22017787] CrossrefMedlineGoogle Scholar
    • 15. Raebel MAEllis JLCarroll NMBayliss EAMcGinnis BSchroeder EBet alCharacteristics of patients with primary non-adherence to medications for hypertension, diabetes, and lipid disorders. J Gen Intern Med2012;27:57-64. [PMID: 21879374] CrossrefMedlineGoogle Scholar
    • 16. Shin JMcCombs JSSanchez RJUdall MDeminski MCCheetham TCPrimary nonadherence to medications in an integrated healthcare setting. Am J Manag Care2012;18:426-34. [PMID: 22928758] MedlineGoogle Scholar
    • 17. Cheetham TCNiu FGreen KScott RDDerose SFVansomphone SSet alPrimary nonadherence to statin medications in a managed care organization. J Manag Care Pharm2013;19:367-73. [PMID: 23697474] CrossrefMedlineGoogle Scholar
    • 18. Reynolds KMuntner PCheetham TCHarrison TNMorisky DESilverman Set alPrimary non-adherence to bisphosphonates in an integrated healthcare setting. Osteoporos Int2013;24:2509-17. [PMID: 23595561] CrossrefMedlineGoogle Scholar
    • 19. Derose SFGreen KMarrett ETunceli KCheetham TCChiu VYet alAutomated outreach to increase primary adherence to cholesterol-lowering medications. JAMA Intern Med2013;173:38-43. [PMID: 23403978] CrossrefMedlineGoogle Scholar
    • 20. Tamblyn RLavoie GPetrella LMonette JThe use of prescription claims databases in pharmacoepidemiological research: the accuracy and comprehensiveness of the prescription claims database in Québec. J Clin Epidemiol1995;48:999-1009. [PMID: 7775999] CrossrefMedlineGoogle Scholar
    • 21. Wilchesky MTamblyn RMHuang AValidation of diagnostic codes in medical services claims data. Can J Clin Pharmacol2001;8:39. Google Scholar
    • 22. Tamblyn RHuang APerreault RJacques ARoy DHanley Jet alThe medical office of the 21st century (MOXXI): effectiveness of computerized decision-making support in reducing inappropriate prescribing in primary care. CMAJ2003;169:549-56. [PMID: 12975221] MedlineGoogle Scholar
    • 23. Eguale TTamblyn RWinslade NBuckeridge DDetection of adverse drug events and other treatment outcomes using an electronic prescribing system. Drug Saf2008;31:1005-16. [PMID: 18840020] CrossrefMedlineGoogle Scholar
    • 24. Eguale TWinslade NHanley JABuckeridge DLTamblyn REnhancing pharmacosurveillance with systematic collection of treatment indication in electronic prescribing: a validation study in Canada. Drug Saf2010;33:559-67. [PMID: 20553057] CrossrefMedlineGoogle Scholar
    • 25. Tamblyn RHuang AKawasumi YBartlett GGrad RJacques Aet alThe development and evaluation of an integrated electronic prescribing and drug management system for primary care. J Am Med Inform Assoc2006;13:148-59. [PMID: 16357357] CrossrefMedlineGoogle Scholar
    • 26. Tamblyn RReidel KHuang ATaylor LWinslade NBartlett Get alIncreasing the detection and response to adherence problems with cardiovascular medication in primary care through computerized drug management systems: a randomized controlled trial. Med Decis Making2010;30:176-88. [PMID: 19675319] CrossrefMedlineGoogle Scholar
    • 27. American Society of Hospital PharmacistsAHFS Drug Information: 2012. Bethesda, MD: American Society of Health-System Pharmacists; 2012. Google Scholar
    • 28. World Health Organization. International Statistical Classification of Diseases and Related Health Problems 10th Revision. 2010. Accessed at http://apps.who.int/classifications/icd10/browse/2010/en on 31 January 2014. Google Scholar
    • 29. Hakim AE-prescribing and primary noncompliance: physician and patient experience. Prof Case Manag2010;15:62-7. [PMID: 20234287] CrossrefMedlineGoogle Scholar
    • 30. Jackevicius CALi PTu JVPrevalence, predictors, and outcomes of primary nonadherence after acute myocardial infarction. Circulation2008;117:1028-36. [PMID: 18299512] CrossrefMedlineGoogle Scholar
    • 31. Briesacher BRoss-Degnan DAdams AWagner AGurwitz JSoumerai SA new measure of medication affordability. Soc Work Public Health2009;24:600-12. [PMID: 19821195] CrossrefMedlineGoogle Scholar
    • 32. Lexchin JGrootendorst PEffects of prescription drug user fees on drug and health services use and on health status in vulnerable populations: a systematic review of the evidence. Int J Health Serv2004;34:101-22. [PMID: 15088676] CrossrefMedlineGoogle Scholar
    • 33. Tamblyn RLaprise RHanley JAAbrahamowicz MScott SMayo Net alAdverse events associated with prescription drug cost-sharing among poor and elderly persons. JAMA2001;285:421-9. [PMID: 11242426] CrossrefMedlineGoogle Scholar
    • 34. Wilkins RUse of postal codes and addresses in the analysis of health data. Health Rep1993;5:157-77. [PMID: 8292756] MedlineGoogle Scholar
    • 35. Charlson MEPompei PAles KLMacKenzie CRA new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis1987;40:373-83. [PMID: 3558716] CrossrefMedlineGoogle Scholar
    • 36. Tamblyn RAbrahamowicz MDauphinee DWenghofer EJacques AKlass Det alInfluence of physicians' management and communication ability on patients' persistence with antihypertensive medication. Arch Intern Med2010;170:1064-72. [PMID: 20585073] CrossrefMedlineGoogle Scholar
    • 37. Ekedahl AMånsson NUnclaimed prescriptions after automated prescription transmittals to pharmacies. Pharm World Sci2004;26:26-31. [PMID: 15018256] CrossrefMedlineGoogle Scholar
    • 38. Ananth CVKantor MLModeling multivariate binary responses with multiple levels of nesting based on alternating logistic regressions: an application to caries aggregation. J Dent Res2004;83:776-81. [PMID: 15381718] CrossrefMedlineGoogle Scholar
    • 39. Carey VZeger SLDiggle PModelling multivariate binary data with alternating logistic regressions. Biometrika1993;80:517-26. CrossrefGoogle Scholar
    • 40. Preisser JSArcury TAQuandt SADetecting patterns of occupational illness clustering with alternating logistic regressions applied to longitudinal data. Am J Epidemiol2003;158:495-501. [PMID: 12936905] CrossrefMedlineGoogle Scholar
    • 41. Fang RKmetic AMillar JDrasic LDisparities in chronic disease among Canada's low-income populations. Prev Chronic Dis2009;6:A115. [PMID: 19754991] MedlineGoogle Scholar
    • 42. Shah NRHirsch AGZacker CTaylor SWood GCStewart WFFactors associated with first-fill adherence rates for diabetic medications: a cohort study. J Gen Intern Med2009;24:233-7. [PMID: 19093157] CrossrefMedlineGoogle Scholar
    • 43. Kraut AWalld RTate RMustard CImpact of diabetes on employment and income in Manitoba, Canada. Diabetes Care2001;24:64-8. [PMID: 11194243] CrossrefMedlineGoogle Scholar
    • 44. Alter DABrandes SIrvine JIron KImpact of socioeconomic status on cardiovascular outcomes in Canada. Expert Rev Pharmacoecon Outcomes Res2003;3:691-702. [PMID: 19807347] CrossrefMedlineGoogle Scholar
    • 45. Banks JMarmot MOldfield ZSmith JPDisease and disadvantage in the United States and in England. JAMA2006;295:2037-45. [PMID: 16670412] CrossrefMedlineGoogle Scholar
    • 46. McWilliams JMMeara EZaslavsky AMAyanian JZDifferences in control of cardiovascular disease and diabetes by race, ethnicity, and education: U.S. trends from 1999 to 2006 and effects of medicare coverage. Ann Intern Med2009;150:505-15. [PMID: 19380852] LinkGoogle Scholar
    • 47. Braveman PACubbin CEgerter SWilliams DRPamuk ESocioeconomic disparities in health in the United States: what the patterns tell us. Am J Public Health2010;100 Suppl 1 S186-96. [PMID: 20147693] CrossrefMedlineGoogle Scholar
    • 48. Cope SFUngar WJGlazier RHSocioeconomic factors and asthma control in children. Pediatr Pulmonol2008;43:745-52. [PMID: 18615669] CrossrefMedlineGoogle Scholar
    • 49. Ungar WJPaterson JMGomes TBikangaga PGold MTo Tet alRelationship of asthma management, socioeconomic status, and medication insurance characteristics to exacerbation frequency in children with asthma. Ann Allergy Asthma Immunol2011;106:17-23. [PMID: 21195940] CrossrefMedlineGoogle Scholar
    • 50. Schuetz BMann EEverett WEducating health professionals collaboratively for team-based primary care. Health Aff (Millwood)2010;29:1476-80. [PMID: 20679650] CrossrefMedlineGoogle Scholar
    • 51. Calman NSGolub MShuman SPrimary care and health reform. Mt Sinai J Med2012;79:527-34. [PMID: 22976358] CrossrefMedlineGoogle Scholar
    • 52. Samuelson MTedeschi PAarendonk Dde la Cuesta CGroenewegen PImproving interprofessional collaboration in primary care: position paper of the European Forum for Primary Care. Qual Prim Care2012;20:303-12. [PMID: 23113915] MedlineGoogle Scholar
    • 53. Haggerty JLReid RJFreeman GKStarfield BHAdair CEMcKendry RContinuity of care: a multidisciplinary review. BMJ2003;327:1219-21. [PMID: 14630762] CrossrefMedlineGoogle Scholar
    • 54. Rosenthal TCThe medical home: growing evidence to support a new approach to primary care. J Am Board Fam Med2008;21:427-40. [PMID: 18772297] CrossrefMedlineGoogle Scholar
    • 55. Zeber JEManias EWilliams AFHutchins DUdezi WARoberts CSet alISPOR Medication Adherence Good Research Practices Working GroupA 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 Health2013;16:891-900. [PMID: 23947984] CrossrefMedlineGoogle Scholar
    • 56. Galea STracy MParticipation rates in epidemiologic studies. Ann Epidemiol2007;17:643-53. [PMID: 17553702] CrossrefMedlineGoogle Scholar
    • 57. Knudsen AKHotopf MSkogen JCOverland SMykletun AThe health status of nonparticipants in a population-based health study: the Hordaland Health Study. Am J Epidemiol2010;172:1306-14. [PMID: 20843863] CrossrefMedlineGoogle Scholar
    • 58. Newhouse JPThe Insurance Experiment GroupFree for All? Lessons from the RAND Health Insurance Experiment. London, UK: Harvard Univ Pr; 1993:8-243. Google Scholar
    • 59. Ayanian JZKohler BAAbe TEpstein AMThe relation between health insurance coverage and clinical outcomes among women with breast cancer. N Engl J Med1993;329:326-31. [PMID: 8321261] CrossrefMedlineGoogle Scholar
    • 60. Schoen CDavis KDesRoches CDonelan KBlendon RHealth insurance markets and income inequality: findings from an international health policy survey. Health Policy2000;51:67-85. [PMID: 10699676] CrossrefMedlineGoogle Scholar
    • 61. Lasser KEHimmelstein DUWoolhandler SAccess to care, health status, and health disparities in the United States and Canada: results of a cross-national population-based survey. Am J Public Health2006;96:1300-7. [PMID: 16735628] CrossrefMedlineGoogle Scholar
    • 62. Todd JArmon CGriggs APoole SBerman SIncreased rates of morbidity, mortality, and charges for hospitalized children with public or no health insurance as compared with children with private insurance in Colorado and the United States. Pediatrics2006;118:577-85. [PMID: 16882810] CrossrefMedlineGoogle Scholar
    • 63. Lexchin J. A National Pharmacare Plan: Combining Efficiency and Equity. Canadian Centre for Policy Alternatives; 2001. Accessed at www.policyalternatives.ca/sites/default/files/uploads/publications/National_Office_Pubs/pharmacare.pdf on 31 January 2014. Google Scholar
    • 64. Hynd ARoughead EEPreen DBGlover JBulsara MSemmens JIncreased patient co-payments and changes in PBS-subsidised prescription medicines dispensed in Western Australia. Aust N Z J Public Health2009;33:246-52. [PMID: 19630844] CrossrefMedlineGoogle Scholar
    • 65. Daw JRMorgan SGStitching the gaps in the Canadian public drug coverage patchwork?: a review of provincial pharmacare policy changes from 2000 to 2010. Health Policy2012;104:19-26. [PMID: 21978939] CrossrefMedlineGoogle Scholar
    • 66. Boothe KHow the pace of change affects the scope of reform: pharmaceutical insurance in Canada, Australia, and the United kingdom. J Health Polit Policy Law2012;37:779-814. [PMID: 22700948] CrossrefMedlineGoogle Scholar
    • 67. McKee MBalabanova DBasu SRicciardi WStuckler DUniversal health coverage: a quest for all countries but under threat in some. Value Health2013;16:S39-45. [PMID: 23317643] CrossrefMedlineGoogle Scholar
    • 68. Kennedy JMorgan SA cross-national study of prescription nonadherence due to cost: data from the Joint Canada-United States Survey of Health. Clin Ther2006;28:1217-24. [PMID: 16982299] CrossrefMedlineGoogle Scholar
    • 69. Goldman DPJoyce GFZheng YPrescription drug cost sharing: associations with medication and medical utilization and spending and health. JAMA2007;298:61-9. [PMID: 17609491] CrossrefMedlineGoogle Scholar
    • 70. Kennedy JMorgan SCost-related prescription nonadherence in the United States and Canada: a system-level comparison using the 2007 International Health Policy Survey in Seven Countries. Clin Ther2009;31:213-9. [PMID: 19243719] CrossrefMedlineGoogle Scholar
    • 71. Law MRCheng LDhalla IAHeard DMorgan SGThe effect of cost on adherence to prescription medications in Canada. CMAJ2012;184:297-302. [PMID: 22249979] CrossrefMedlineGoogle Scholar
    • 72. Localio ARBerlin JATen Have TRKimmel SEAdjustments for center in multicenter studies: an overview. Ann Intern Med2001;135:112-23. [PMID: 11453711] LinkGoogle Scholar