Abstract
Background:
Primary nonadherence is probably an important contributor to suboptimal disease management, but methodological challenges have limited investigation of it.
Objective:
To estimate the incidence of primary nonadherence in primary care and the drug, patient, and physician characteristics that are associated with nonadherence.
Design:
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.
Setting:
Quebec, Canada.
Patients:
15 961 patients in a primary care network of 131 physicians.
Measurements:
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.
Results:
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]).
Limitation:
Patients' rationale for choosing not to fill their prescriptions could not be measured.
Conclusion:
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.
References
- 1.
Halpin HA ,Morales-Suárez-Varela MM ,Martin-Moreno JM . Chronic disease prevention and the new public health. Public Health Rev. 2010;32:120-54. CrossrefGoogle Scholar - 2.
Daar AS ,Singer PA ,Persad DL ,Pramming SK ,Matthews DR ,Beaglehole R ,et al . Grand challenges in chronic non-communicable diseases. Nature. 2007;450:494-6. [PMID: 18033288] CrossrefMedlineGoogle Scholar - 3.
van der Linden CM ,Jansen PA ,van Geerenstein EV ,van Marum RJ ,Grouls RJ ,Egberts TC ,et al . Reasons for discontinuation of medication during hospitalization and documentation thereof: a descriptive study of 400 geriatric and internal medicine patients [Letter]. Arch Intern Med. 2010;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 PM ,Bryson CL ,Rumsfeld JS . Medication adherence: its importance in cardiovascular outcomes. Circulation. 2009;119:3028-35. [PMID: 19528344] CrossrefMedlineGoogle Scholar - 6.
Yang Y ,Thumula V ,Pace PF ,Banahan BF ,Wilkin NE ,Lobb WB . Medication nonadherence and the risks of hospitalization, emergency department visits, and death among Medicare Part D enrollees with diabetes. Drug Benefit Trends. 2009;21:330-8. Google Scholar - 7.
Halm EA ,Mora P ,Leventhal H . No symptoms, no asthma: the acute episodic disease belief is associated with poor self-management among inner-city adults with persistent asthma. Chest. 2006;129:573-80. [PMID: 16537854] CrossrefMedlineGoogle Scholar - 8.
Solomon MD ,Majumdar SR . Primary non-adherence of medications: lifting the veil on prescription-filling behaviors [Editorial]. J Gen Intern Med. 2010;25:280-1. [PMID: 20195783] CrossrefMedlineGoogle Scholar - 9.
Jackevicius CA ,Mamdani M ,Tu JV . Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA. 2002;288:462-7. [PMID: 12132976] CrossrefMedlineGoogle Scholar - 10.
Storm A ,Andersen SE ,Benfeldt E ,Serup J . One in 3 prescriptions are never redeemed: primary nonadherence in an outpatient clinic. J Am Acad Dermatol. 2008;59:27-33. [PMID: 18467003] CrossrefMedlineGoogle Scholar - 11.
Shah NR ,Hirsch AG ,Zacker C ,Wood GC ,Schoenthaler A ,Ogedegbe G ,et al . Predictors of first-fill adherence for patients with hypertension. Am J Hypertens. 2009;22:392-6. [PMID: 19180061] CrossrefMedlineGoogle Scholar - 12.
Ko DT ,Chiu M ,Guo H ,Austin PC ,Marquis JF ,Tu JV . Patterns of use of thienopyridine therapy after percutaneous coronary interventions with drug-eluting stents and bare-metal stents. Am Heart J. 2009;158:592-598.e1. [PMID: 19781419] CrossrefMedlineGoogle Scholar - 13.
Fischer MA ,Stedman MR ,Lii J ,Vogeli C ,Shrank WH ,Brookhart MA ,et al . Primary medication non-adherence: analysis of 195,930 electronic prescriptions. J Gen Intern Med. 2010;25:284-90. [PMID: 20131023] CrossrefMedlineGoogle Scholar - 14.
Fischer MA ,Choudhry NK ,Brill G ,Avorn J ,Schneeweiss S ,Hutchins D ,et al . Trouble getting started: predictors of primary medication nonadherence. Am J Med. 2011;124:1081.e9-22. [PMID: 22017787] CrossrefMedlineGoogle Scholar - 15.
Raebel MA ,Ellis JL ,Carroll NM ,Bayliss EA ,McGinnis B ,Schroeder EB ,et al . Characteristics of patients with primary non-adherence to medications for hypertension, diabetes, and lipid disorders. J Gen Intern Med. 2012;27:57-64. [PMID: 21879374] CrossrefMedlineGoogle Scholar - 16.
Shin J ,McCombs JS ,Sanchez RJ ,Udall M ,Deminski MC ,Cheetham TC . Primary nonadherence to medications in an integrated healthcare setting. Am J Manag Care. 2012;18:426-34. [PMID: 22928758] MedlineGoogle Scholar - 17.
Cheetham TC ,Niu F ,Green K ,Scott RD ,Derose SF ,Vansomphone SS ,et al . Primary nonadherence to statin medications in a managed care organization. J Manag Care Pharm. 2013;19:367-73. [PMID: 23697474] CrossrefMedlineGoogle Scholar - 18.
Reynolds K ,Muntner P ,Cheetham TC ,Harrison TN ,Morisky DE ,Silverman S ,et al . Primary non-adherence to bisphosphonates in an integrated healthcare setting. Osteoporos Int. 2013;24:2509-17. [PMID: 23595561] CrossrefMedlineGoogle Scholar - 19.
Derose SF ,Green K ,Marrett E ,Tunceli K ,Cheetham TC ,Chiu VY ,et al . Automated outreach to increase primary adherence to cholesterol-lowering medications. JAMA Intern Med. 2013;173:38-43. [PMID: 23403978] CrossrefMedlineGoogle Scholar - 20.
Tamblyn R ,Lavoie G ,Petrella L ,Monette J . The use of prescription claims databases in pharmacoepidemiological research: the accuracy and comprehensiveness of the prescription claims database in Québec. J Clin Epidemiol. 1995;48:999-1009. [PMID: 7775999] CrossrefMedlineGoogle Scholar - 21.
Wilchesky M ,Tamblyn RM ,Huang A . Validation of diagnostic codes in medical services claims data. Can J Clin Pharmacol. 2001;8:39. Google Scholar - 22.
Tamblyn R ,Huang A ,Perreault R ,Jacques A ,Roy D ,Hanley J ,et al . The medical office of the 21st century (MOXXI): effectiveness of computerized decision-making support in reducing inappropriate prescribing in primary care. CMAJ. 2003;169:549-56. [PMID: 12975221] MedlineGoogle Scholar - 23.
Eguale T ,Tamblyn R ,Winslade N ,Buckeridge D . Detection of adverse drug events and other treatment outcomes using an electronic prescribing system. Drug Saf. 2008;31:1005-16. [PMID: 18840020] CrossrefMedlineGoogle Scholar - 24.
Eguale T ,Winslade N ,Hanley JA ,Buckeridge DL ,Tamblyn R . Enhancing pharmacosurveillance with systematic collection of treatment indication in electronic prescribing: a validation study in Canada. Drug Saf. 2010;33:559-67. [PMID: 20553057] CrossrefMedlineGoogle Scholar - 25.
Tamblyn R ,Huang A ,Kawasumi Y ,Bartlett G ,Grad R ,Jacques A ,et al . The development and evaluation of an integrated electronic prescribing and drug management system for primary care. J Am Med Inform Assoc. 2006;13:148-59. [PMID: 16357357] CrossrefMedlineGoogle Scholar - 26.
Tamblyn R ,Reidel K ,Huang A ,Taylor L ,Winslade N ,Bartlett G ,et al . Increasing the detection and response to adherence problems with cardiovascular medication in primary care through computerized drug management systems: a randomized controlled trial. Med Decis Making. 2010;30:176-88. [PMID: 19675319] CrossrefMedlineGoogle Scholar - 27.
American Society of Hospital Pharmacists . AHFS 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 A . E-prescribing and primary noncompliance: physician and patient experience. Prof Case Manag. 2010;15:62-7. [PMID: 20234287] CrossrefMedlineGoogle Scholar - 30.
Jackevicius CA ,Li P ,Tu JV . Prevalence, predictors, and outcomes of primary nonadherence after acute myocardial infarction. Circulation. 2008;117:1028-36. [PMID: 18299512] CrossrefMedlineGoogle Scholar - 31.
Briesacher B ,Ross-Degnan D ,Adams A ,Wagner A ,Gurwitz J ,Soumerai S . A new measure of medication affordability. Soc Work Public Health. 2009;24:600-12. [PMID: 19821195] CrossrefMedlineGoogle Scholar - 32.
Lexchin J ,Grootendorst P . Effects 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 Serv. 2004;34:101-22. [PMID: 15088676] CrossrefMedlineGoogle Scholar - 33.
Tamblyn R ,Laprise R ,Hanley JA ,Abrahamowicz M ,Scott S ,Mayo N ,et al . Adverse events associated with prescription drug cost-sharing among poor and elderly persons. JAMA. 2001;285:421-9. [PMID: 11242426] CrossrefMedlineGoogle Scholar - 34.
Wilkins R . Use of postal codes and addresses in the analysis of health data. Health Rep. 1993;5:157-77. [PMID: 8292756] MedlineGoogle Scholar - 35.
Charlson ME ,Pompei P ,Ales KL ,MacKenzie CR . A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373-83. [PMID: 3558716] CrossrefMedlineGoogle Scholar - 36.
Tamblyn R ,Abrahamowicz M ,Dauphinee D ,Wenghofer E ,Jacques A ,Klass D ,et al . Influence of physicians' management and communication ability on patients' persistence with antihypertensive medication. Arch Intern Med. 2010;170:1064-72. [PMID: 20585073] CrossrefMedlineGoogle Scholar - 37.
Ekedahl A ,Månsson N . Unclaimed prescriptions after automated prescription transmittals to pharmacies. Pharm World Sci. 2004;26:26-31. [PMID: 15018256] CrossrefMedlineGoogle Scholar - 38.
Ananth CV ,Kantor ML . Modeling multivariate binary responses with multiple levels of nesting based on alternating logistic regressions: an application to caries aggregation. J Dent Res. 2004;83:776-81. [PMID: 15381718] CrossrefMedlineGoogle Scholar - 39.
Carey V ,Zeger SL ,Diggle P . Modelling multivariate binary data with alternating logistic regressions. Biometrika. 1993;80:517-26. CrossrefGoogle Scholar - 40.
Preisser JS ,Arcury TA ,Quandt SA . Detecting patterns of occupational illness clustering with alternating logistic regressions applied to longitudinal data. Am J Epidemiol. 2003;158:495-501. [PMID: 12936905] CrossrefMedlineGoogle Scholar - 41.
Fang R ,Kmetic A ,Millar J ,Drasic L . Disparities in chronic disease among Canada's low-income populations. Prev Chronic Dis. 2009;6:A115. [PMID: 19754991] MedlineGoogle Scholar - 42.
Shah NR ,Hirsch AG ,Zacker C ,Taylor S ,Wood GC ,Stewart WF . Factors associated with first-fill adherence rates for diabetic medications: a cohort study. J Gen Intern Med. 2009;24:233-7. [PMID: 19093157] CrossrefMedlineGoogle Scholar - 43.
Kraut A ,Walld R ,Tate R ,Mustard C . Impact of diabetes on employment and income in Manitoba, Canada. Diabetes Care. 2001;24:64-8. [PMID: 11194243] CrossrefMedlineGoogle Scholar - 44.
Alter DA ,Brandes S ,Irvine J ,Iron K . Impact of socioeconomic status on cardiovascular outcomes in Canada. Expert Rev Pharmacoecon Outcomes Res. 2003;3:691-702. [PMID: 19807347] CrossrefMedlineGoogle Scholar - 45.
Banks J ,Marmot M ,Oldfield Z ,Smith JP . Disease and disadvantage in the United States and in England. JAMA. 2006;295:2037-45. [PMID: 16670412] CrossrefMedlineGoogle Scholar - 46.
McWilliams JM ,Meara E ,Zaslavsky AM ,Ayanian JZ . Differences 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 Med. 2009;150:505-15. [PMID: 19380852] LinkGoogle Scholar - 47.
Braveman PA ,Cubbin C ,Egerter S ,Williams DR ,Pamuk E . Socioeconomic disparities in health in the United States: what the patterns tell us. Am J Public Health. 2010;100Suppl 1 S186-96. [PMID: 20147693] CrossrefMedlineGoogle Scholar - 48.
Cope SF ,Ungar WJ ,Glazier RH . Socioeconomic factors and asthma control in children. Pediatr Pulmonol. 2008;43:745-52. [PMID: 18615669] CrossrefMedlineGoogle Scholar - 49.
Ungar WJ ,Paterson JM ,Gomes T ,Bikangaga P ,Gold M ,To T ,et al . Relationship of asthma management, socioeconomic status, and medication insurance characteristics to exacerbation frequency in children with asthma. Ann Allergy Asthma Immunol. 2011;106:17-23. [PMID: 21195940] CrossrefMedlineGoogle Scholar - 50.
Schuetz B ,Mann E ,Everett W . Educating health professionals collaboratively for team-based primary care. Health Aff (Millwood). 2010;29:1476-80. [PMID: 20679650] CrossrefMedlineGoogle Scholar - 51.
Calman NS ,Golub M ,Shuman S . Primary care and health reform. Mt Sinai J Med. 2012;79:527-34. [PMID: 22976358] CrossrefMedlineGoogle Scholar - 52.
Samuelson M ,Tedeschi P ,Aarendonk D ,de la Cuesta C ,Groenewegen P . Improving interprofessional collaboration in primary care: position paper of the European Forum for Primary Care. Qual Prim Care. 2012;20:303-12. [PMID: 23113915] MedlineGoogle Scholar - 53.
Haggerty JL ,Reid RJ ,Freeman GK ,Starfield BH ,Adair CE ,McKendry R . Continuity of care: a multidisciplinary review. BMJ. 2003;327:1219-21. [PMID: 14630762] CrossrefMedlineGoogle Scholar - 54.
Rosenthal TC . The medical home: growing evidence to support a new approach to primary care. J Am Board Fam Med. 2008;21:427-40. [PMID: 18772297] CrossrefMedlineGoogle Scholar - 55.
Zeber JE ,Manias E ,Williams AF ,Hutchins D ,Udezi WA ,Roberts CS ,et al ;ISPOR Medication Adherence Good Research Practices Working Group . 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. [PMID: 23947984] CrossrefMedlineGoogle Scholar - 56.
Galea S ,Tracy M . Participation rates in epidemiologic studies. Ann Epidemiol. 2007;17:643-53. [PMID: 17553702] CrossrefMedlineGoogle Scholar - 57.
Knudsen AK ,Hotopf M ,Skogen JC ,Overland S ,Mykletun A . The health status of nonparticipants in a population-based health study: the Hordaland Health Study. Am J Epidemiol. 2010;172:1306-14. [PMID: 20843863] CrossrefMedlineGoogle Scholar - 58.
Newhouse JP ;The Insurance Experiment Group . Free for All? Lessons from the RAND Health Insurance Experiment. London, UK: Harvard Univ Pr; 1993:8-243. Google Scholar - 59.
Ayanian JZ ,Kohler BA ,Abe T ,Epstein AM . The relation between health insurance coverage and clinical outcomes among women with breast cancer. N Engl J Med. 1993;329:326-31. [PMID: 8321261] CrossrefMedlineGoogle Scholar - 60.
Schoen C ,Davis K ,DesRoches C ,Donelan K ,Blendon R . Health insurance markets and income inequality: findings from an international health policy survey. Health Policy. 2000;51:67-85. [PMID: 10699676] CrossrefMedlineGoogle Scholar - 61.
Lasser KE ,Himmelstein DU ,Woolhandler S . Access to care, health status, and health disparities in the United States and Canada: results of a cross-national population-based survey. Am J Public Health. 2006;96:1300-7. [PMID: 16735628] CrossrefMedlineGoogle Scholar - 62.
Todd J ,Armon C ,Griggs A ,Poole S ,Berman S . Increased 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. Pediatrics. 2006;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 A ,Roughead EE ,Preen DB ,Glover J ,Bulsara M ,Semmens J . Increased patient co-payments and changes in PBS-subsidised prescription medicines dispensed in Western Australia. Aust N Z J Public Health. 2009;33:246-52. [PMID: 19630844] CrossrefMedlineGoogle Scholar - 65.
Daw JR ,Morgan SG . Stitching the gaps in the Canadian public drug coverage patchwork?: a review of provincial pharmacare policy changes from 2000 to 2010. Health Policy. 2012;104:19-26. [PMID: 21978939] CrossrefMedlineGoogle Scholar - 66.
Boothe K . How the pace of change affects the scope of reform: pharmaceutical insurance in Canada, Australia, and the United kingdom. J Health Polit Policy Law. 2012;37:779-814. [PMID: 22700948] CrossrefMedlineGoogle Scholar - 67.
McKee M ,Balabanova D ,Basu S ,Ricciardi W ,Stuckler D . Universal health coverage: a quest for all countries but under threat in some. Value Health. 2013;16:S39-45. [PMID: 23317643] CrossrefMedlineGoogle Scholar - 68.
Kennedy J ,Morgan S . A cross-national study of prescription nonadherence due to cost: data from the Joint Canada-United States Survey of Health. Clin Ther. 2006;28:1217-24. [PMID: 16982299] CrossrefMedlineGoogle Scholar - 69.
Goldman DP ,Joyce GF ,Zheng Y . Prescription drug cost sharing: associations with medication and medical utilization and spending and health. JAMA. 2007;298:61-9. [PMID: 17609491] CrossrefMedlineGoogle Scholar - 70.
Kennedy J ,Morgan S . Cost-related prescription nonadherence in the United States and Canada: a system-level comparison using the 2007 International Health Policy Survey in Seven Countries. Clin Ther. 2009;31:213-9. [PMID: 19243719] CrossrefMedlineGoogle Scholar - 71.
Law MR ,Cheng L ,Dhalla IA ,Heard D ,Morgan SG . The effect of cost on adherence to prescription medications in Canada. CMAJ. 2012;184:297-302. [PMID: 22249979] CrossrefMedlineGoogle Scholar - 72.
Localio AR ,Berlin JA ,Ten Have TR ,Kimmel SE . Adjustments for center in multicenter studies: an overview. Ann Intern Med. 2001;135:112-23. [PMID: 11453711] LinkGoogle Scholar
Author, Article, and Disclosure Information
Robyn Tamblyn,
From the Clinical and Health Informatics Research Group, McGill University, Montreal, Quebec, and University of Ottawa and The Ottawa Hospital, Ottawa, Ontario, Canada.
Acknowledgment: The authors thank Dr. Jim Hanley for his thoughtful suggestions about the statistical analysis and its interpretation and Sherry Shi for her assistance in data analysis.
Grant Support: Dr. Eguale was supported by the Canadian Institutes of Health Research Fellowship.
Disclosures: None disclosed. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-1705.
Reproducible Research Statement: Study protocol and data set: Available from Dr. Tamblyn (e-mail, robyn.
Corresponding Author: Robyn Tamblyn, PhD, McGill University, Morrice House, 1140 Pine Avenue West, Montreal, Quebec H3A 1A3, Canada; e-mail, robyn.
Current Author Addresses: Drs. Tamblyn, Eguale, and Huang; Ms. Winslade; and Ms. Doran: McGill University, Morrice House, 1140 Pine Avenue West, Montreal, Quebec H3A 1A3, Canada.
Author Contributions: Conception and design: R. Tamblyn, T. Eguale, A. Huang, N. Winslade.
Analysis and interpretation of the data: R. Tamblyn, T. Eguale, N. Winslade.
Drafting of the article: R. Tamblyn, T. Eguale, P. Doran.
Critical revision of the article for important intellectual content: R. Tamblyn, T. Eguale, A. Huang, P. Doran.
Final approval of the article: R. Tamblyn, T. Eguale, A. Huang, N. Winslade, P. Doran.
Provision of study materials or patients: R. Tamblyn.
Statistical expertise: R. Tamblyn, T. Eguale.
Obtaining of funding: R. Tamblyn.
Administrative, technical, or logistic support: R. Tamblyn, P. Doran.
Collection and assembly of data: R. Tamblyn, T. Eguale, A. Huang.
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