Adherence to therapy Kamlesh Khunti University of Leicester, UK William Polonsky University of California San Diego, USA 1
Dualities of interest Kamlesh Khunti: Honoraria for speaking, advising or research from AstraZeneca Pharmaceuticals LP, Bristol- Myers Squibb Company, Eli Lilly and Company, Janssen, Merck Sharp & Dohme Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk, Boehringer Ingelheim, Roche and Sanofi William Polonsky: Honoraria for speaking, advising or research from Sanofi, Novo Nordisk, Lilly, Dexcom, Abbott Diabetes Care, Roche Diagnostics, Bayer Diabetes Care, Amylin and GlaxoSmithKline. GLB-DIA 14.04.61 2
Objectives of this workshop Discuss the definition of adherence Discuss the following questions: How do you ask/assess medication adherence in your patients? What do you feel are the key reasons for medication non-adherence in your patients? What effective strategies have you discovered for addressing poor medication adherence? 3
Components of adherence and established measures Adherence has two separate components Compliance is the degree to which a patient correctly follows medical advice For example, administering the right number of injections each day Persistence is a measure of the duration for which the patient remains compliant Common measures of adherence include: Medication possession ratio (MPR) Calculated using prescription-claims data Total number of days that prescriptions are supplied for in the analysis period divided by the total number of days in the analysis period Proportion of days covered Number of days during the analysis period for which the patient is covered (i.e. has access to medication) divided by the total number of days in the analysis period] Many studies use self-administered questionnaires to obtain measures of adherence; the methodology of these questionnaires can vary enormously Davies MJ, et al. Diabet Med 2013;30:512 24. 4
The adherence problem MPR < 80% is considered as poorly adherent Kaiser Permanente, T2DM n = 9377: 30% poorly adherent to >1 cardiometabolic medication VHA National Database, T2DM n = 740,195: 42% poorly adherent to >1 hypoglycemic agent 5
Poor adherence is common and associated with adverse outcomes 21% patients with diabetes were poorly adherent Poor adherence was associated with lower target achievement and increased hospitalization and mortality Adherent patients Non-adherent patients P value All-cause mortality, % 4.0 5.9 <0.001 All-cause hospitalizations, % 19.2 23.2 <0.001 Mean (SD) HbA 1C, % 7.7 (1.5) 8.1 (1.9) <0.001 Mean systolic BP, mmhg 131 132 0.09 Mean diastolic BP, mmhg 74 76 <0.001 Mean LDL-C, mg/dl 85.5 98 <0.001 Retrospective cohort study 11,532 patients with diabetes in a managed care organization Ho PM et al. Arch Intern Med. 2006;166:1836-41 6
Poor adherence is associated with poor glycemic control In a Japanese study, 29% reported less than optimal adherence Good good glycemic control (HbA 1C <7%) was associated with fewer missed injections Never missed insulin injections Seldom missed insulin injections Missed insulin injections less than half of the time to always P value HbA 1C, % 7.6 8.0 9.4 <0.001 Adjusted RRs for good glycemic control (95% CI) 1.00 0.82 (0.67 1.00) 0.64 (0.31 1.31) 0.029 DDCRT 3 1,441 patients with T2DM who were treated with insulin in a diabetes registry in Japan DDCRT 3, Diabetes Distress and Care Registry at Tenri Mashitani T et al. Diabetes Res Clin Pract. 2013;100:189-94 7
Poor adherence is associated with increased costs Poor medication adherence in diabetes was associated with 37% lower pharmacy costs and 7% lower outpatient costs, but 41% higher inpatient costs Improving adherence would result in annual estimated cost savings of $661 million to $1.16 billion Inpatient cost, $1,000 Analysis of US Veterans with T2DM N=740,165 Followed from 2002 to 2006 or until lost to follow up 18 16 14 12 10 8 6 4 2 Adherence, medication possession ratio 0.8 Non-adherence, medication possession ratio <0.8 0 2002 2003 2004 2005 2006 Fiscal year Egede LE, et al. Diabetes Care 2012;35:2533 2539 8
Among YOUR diabetes patients, how common is poor medication adherence? A Less than 10% of my patients B C D E F 11 20% 21 30% 31 40% 41 50% More than half of my patients 9
How do you ask/assess medication adherence in your patients?
What do you feel are the key reasons for medication non-adherence in your patients?
Medication obstacles Forgetfulness Depression Treatment complexity Medication costs Patient-provider trust Beliefs about diabetes and medications 12
Depression and medication use Comparing depressed vs non-depressed patients with diabetes: More likely to omit insulin Twice as likely to be skipping OHAs Depressed patients evidence 20% fewer days of adequate OHA medication coverage More likely to be skipping antihypertensive and lipid-lowering medicines Polonsky WH, et al. Diabetes Spectrum. 2000;13:36-41. (C) Ciechanowski PS, et al. Arch Intern Med. 2000;160:3278-3285. (B) Kilbourne AM, et al. Am J Geriatr Psychiatry. 2005;13:202-210. (B) Kalsekar ID, et al. Ann Pharmacother. 2006;40:605-611. (B) Lin EH, et al. Diabetes Care. 2004;27:2154-2160. (B) 13
% of Days Medication Taken Properly Treatment complexity 80 60 Once Twice Thrice 40 20 0 Paes AH, et al. Diabetes Care. 1997;20:1512-1517. (B) 14
Physician-patient relationship Relationship Between Consultation Attributes and Compliance With Medications (the Dependent Variable) in logistic Regression Analysis (N=172) Consultation variable Unadjusted OR (95% CI) Adjusted* OR (95% CI) Trust in physician scale score 1.07 (1.02-1.12) 1.04 (0.99-1.10) Continuity of care UPC index 0.90 (0.97-1.01) 0.99 (0.97-1.02) Usual source of care 2.87 (0.86-9.60) 5.98 (1.88-19.03) Length of care with same doctor 0.94 (0.74-1.19) 0.86 (0.68-1.09) Importance of seeing same doctor each visit 0.86 (0.56-1.30) 0.80 (0.51-1.25) Enablement index 1.03 (0.99-1.08) 1.05 (0.98-1.12) Physician-patient concordance score 1.21 (1.05-1.39) 1.34 (1.04-1.72) Kerse et al, 2004 15
What does trust mean? To what extent do you think the doctor understands why you came in today? How well do you think the doctor understood you today? To what extent did you and the doctor agree about the main problem or need today? To what extent did you and the doctor agree about what to do about the problem or need?
Patients medication beliefs Adherence is better when medication is perceived as worth the effort Dosage must be sufficient Patients must know why they are taking their medications, and how to take them Perceived gain must outweigh perceived cost including side-effects 17
Among YOUR patients, what is the main contributor to poor insulin adherence? A Forgetfulness B C D E F G Depression Treatment complexity Medication costs Patient-provider trust Beliefs about diabetes and medications Something else! 18
What effective strategies have you discovered for addressing poor medication adherence?
Predictive factors for adherence to insulin and strategies for improving adherence to insulin Positive predictors of adherence to insulin Changing insulin therapy Switching from a vial/syringe to a pen device Initiating insulin therapy with a pen device instead of a vial/syringe Changing type of insurance plan Switching from a traditional formulary scheme to a value-based insurance design Predictive factors for adherence to insulin Negative predictors of adherence to insulin Switching from a vial/syringe to a pen device Strategies for improving adherence Increased use/availability of pen devices Reduce the financial burden of insulin therpy to the patient Older age Support from a diabetic nurse specialist Physical disability Higher household income Following a healthy diet Perceived self-efficacy Hypoglycemia awareness Previous experience of liaison psychiatry Previous experience of cognitive behavioural therapy Patient-perceived barriers to insulin adherence Lower perceived consequences of diabetes Higher perception of personal control Older age Female gender Single status Lower HbA 1c levels Being a student Having the highest level of education Needing a large number of injections Type 2 diabetes (vs. type 1) Provide additional medical support to patients (e.g. nurses, psychiatrists) Educational programmes to increase awareness of diabetes Develop therapies that allow for fewer injections and increased flexibility in treatment regimen Provide additional medical support to patients (e.g. nurses, psychiatrists) Davies MJ, et al. Diabet Med 2013;30:512 24. 20
A1C Anchoring medication to daily events 8.00 Anchors Does not anchor 7.00 6.00 A daily event (a meal, TV show, bedtime, brushing my teeth) reminds me. Littenberg B, et al. BMC Fam Prac. 2006;7:1. (B) 21
Meta-analysis of RCTs to improve medication adherence 69 RCT s, multiple chronic illness conditions Most intervention have been shown to enhance adherence, but: Even the most effective interventions did not lead to large improvements in adherence and treatment outcomes. Haynes et al, Cochrane Database Syst Rev. 2008 Apr 16;(2):CD000011
Change in HbA 1c (%) Educational interventions to overcome hypoglycaemia 0.4 Baseline 6 months 12 months 18 months 0.2 0-0.2-0.4-0.6-0.8-1 -1.2 Overall effect: 0.48 ( 0.76 to 0.21), p=0.001 Intervention Control Crasto W et al. Diabet Res Clin Pract 2011;93:328-36.
Hypoglycaemic events Events Intensive group Control group P value Hypoglycaemic event, n(%) Grade 1 (mild) 39 (42.4) 31 (32.5) 0.52 Grade 2 (moderate) 11 (11.2) 27 (29) < 0.05 Grade 3 (severe) 0 6 (6.3) 0.06 Crasto et al. Diabet Res Clin Pract 2011;93(3):328-36
Four medication secrets 1. Taking your medications is one of the most powerful things you can do to positively affect your health 2. Your medications are working even if you can t feel it 3. Needing more medication isn t your fault 4. More medication doesn t mean you are sicker, less medication doesn t mean you are healthier 25
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