CPD 40: MEDICATION ADHERENCE IN CHRONIC DISEASE Biography - Margaret Bermingham is a research pharmacist in the Heart Failure Unit, St Michael’s Hospital and St Vincent’s University Hospital, Dublin and I work in conjunction with the St Vincent’s Screening to Prevent Heart Failure team. In 2013, I completed a PhD in pharmaceutical care in heart failure in the School of Medicine and Medical Science, UCD. My research interests include heart failure prevention; inappropriate prescribing and medication adherence in cardiovascular disease.
Module 1 June 2012
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Medication Adherence in Chronic Disease
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Sheehan et al reported in 1996 that the estimated cost of Patient pain for 95 patients to the Irish Health Services when added adherence Pain is one of the commonest reasons for patients to seek is of theSocial extent to the amount Welfare payments received and 1 medical attention. A recent survey has shown that as many to which the lost earnings of each patient amounted to 1.9 million as 8.3 visits per year to primary care physicians in Ireland a person’s appreciate the long-term consequencespounds of non- at the INTRODUCTION time of referral.6 The recent data from PRIME 2 behaviour, were due to symptoms of pain. A large scale survey carried adherence to therapies for non-symptomatic survey showsuch that the as mean cost per chronic pain patient Managing adherence to out medication in chronic disease such in as2006, hypertension. However older in 15 European countries and Israel screening taking, disease is an ongoing challenge for both the is estimated medication at €5,665 per year across all grades of pain, patients may have difficulties remembering 46,394 respondents that the prevalence of chronic patient and the healthcare provider. Indeed reported corresponds agreed to take a medicine or managing complexwhich was extrapolated to with €5.34 billion or 2.86% of Irish pain of moderate intensity inEconomic adult Europeans was between it has been estimated that adherence to to severeregimens. recommendations from a healthcare factors differ 7 GDP per year. This demonstrates an urgent need for cost therapies for chronic disease provider. The term adherence is settings and while we often think solely of 19%.3is no greater effective strategies to manage chronic pain effectively. than 50%.1 Patient adherence is the extent generally preferred to compliance as the cost of medication affecting adherence to which a person’s behaviour, such as (or persistence), overall healthcare costs, the the former suggests a contract between More recent survey data from another study, carried out medication taking, corresponds with agreed patient’s ability to access care i.e. transport to the patient and healthcare provider 2,019 people with 1chronic pain and 1,472 primary chronic pain recommendations from in a healthcare provider. appointments and pharmacy and family Understanding support whereas the latter suggests a patient The term adherence is generally preferred to care physicians across 15 European have also play acountries, role. Finally, consideration must instructions. Chronic painpassively is defined following as pain that outlasts normal healing compliance as the former suggests a contract given to patients chaotic lifestyles for demonstrated that chronic be pain affects 12-54%with of adult time (usually three to six months), and is most frequently between the patient and healthcare provider whom remembering Europeans, its prevalence in Ireland is up toappointments 13%.2 The or taking A major challenge in monitoring whereas the latter suggests a patientand passively medicines as scheduled can be difficult.associated with musculoskeletal disorders such as low medication adherence is identifying PRIME (Prevalence, following instructions.2 Medication adherenceImpact and Cost of Chronic Pain) study, back pain and arthritis. However, it can also be associated useful tools for assessing adherence refers to day-to-day medicines takinghand, and determined (ii) Health system factors: on the other the prevalence of chronic in everyday practice. In clinical trials, with other disorders such as depression or metabolic includes timing, dose and frequency.3 Another pain to be as high as 35.5% in Ireland.4 The PRIME study as directly observed term commonly used is persistence which A number of issues in the patient’s healthcare disorders or methods neurologicsuch conditions such as multiple was the prevalence chronic pain therapy, measurement of a drug or its refers to the continuation of adesigned medicinetoforinvestigate the system may affectofmedication adherence: sclerosis. 3 metabolites in the blood or pill counts prescribed duration of therapy. the communication skills health of the prescriber in Ireland; compare the psychological and physical may be used. or pharmacist; training received by the profiles of those with and without chronic the pain; and explore Pain CAUSES OF NON-ADHERENCE provider in identification of non-adherence or (acute or chronic) can be categorised as nociceptive 4 pain-related disability. Responses to survey questions Nociceptive pain is caused by an active adherence interventions; timewere resourcesor forneuropathic. Practical solutions may be offered to Adherence is a complex,obtained multi-factorial from 1,204 people. the provider; systems that impede information illness, injury and/or inflammatory process associated with 4 patients who have diffi culty adhering to behaviour. The World Health Organisation sharing between settings and co-payment medication. Dispensing medicines in a actual or potential tissue damage i.e. Nociceptive pain (WHO) has described 5 dimensions of 2,4 schemes for chronic supply of medicines. Poor Despite the magnitude of the problem, pain is pill organiser (“dosette or blister adherence: (i) social and economic factors; (ii) results from activity in neural pathwaysbox”) secondary to actual communication between care settings may 2,5 both under-recognised packaging may help patients who forget health system factors; (iii) condition factors; (iv) and undertreated in primary care. lead to unintentional non-persistence when a or potential tissue damage. Nociceptive pain is mediated to take their medicines or forget what therapy related factors and (v) patient Indeed, up to factors. 38% of1patients reported being medicine is lost off ainadequately prescription but may byalso pain receptors located in skin, musculoskeletal system, time they should take their medicines. 2 lead to pain loss of confidenceInon the patient’s part managed in primary care for their symptoms. (i) Social and economic factors: This8 may be especially helpful where bone, and joints. Neuropathic pain, on the other hand, with providers. addition, people with chronic pain reported waiting up to the patient has many doses or a sensory results from direct injury to a peripheral or central Social factors that are associated with non- seeking help and diagnosis, and 1.9 2.2 years between large number of medicines to take (iii) Condition factors nerve; the affected nerves do not produce transduction at adherence include age, gender, socioeconomic throughout the day. years before their pain was adequately managed.2 status and race.4 Younger patients may not nociceptors.8 Pain characteristics and associated conditions The presence of an asymptomatic disease for both types of pain are shown in Table 1. use by Healthcare Professionals in the Republic of Ireland only Learning, Evaluation,For Accredited, Readers, Network | www.learninpharmacy.ie © Copyright 2012 Pfizer Healthcare Ireland Date of Preparation: Module 1 June 2012 EPBU/2012/XXX
CPD 40: MEDICATION ADHERENCE IN CHRONIC DISEASE
adherence is identifying useful tools for assessing adherence in everyday practice. In clinical trials, methods such as directly observed therapy, measurement of a drug or its metabolites in the blood or pill counts may be used. Electronic monitoring systems are used in clinical trial and clinical settings and are considered the closest measure to gold standard. However these are expensive for practitioners and intrusive for patients. In clinical practice quick, inexpensive methods such as patient self-report or use of prescription refill data are more practical.
Module 1 June 2012
sionals in Ireland
anagement in primary care
SELF-REPORT ADHERENCE MEASURES
Providing reminders has been shown effective in improving patient adherence
such as hypertension and high cholesterol is a
ehan et strong al reported in 1996 that the estimated cost of2 predictor of medication non-adherence. Patients with such conditions are at risk of added n for 95 patients to the Irish Health Services when non-adherence as they do not experience he amount of Social Welfare payments received and any symptoms with their condition and may lost earnings of each patient amounted to 1.9 million not believe they require chronic medication. Levels with medication are nds at the timeofofnon-persistence referral.6 The recent data from PRIME both of these with vey showhigh thatinthe mean cost conditions. per chronicPatients pain patient symptomatic disease may be more adherent stimatedtoatsymptom €5,665 per year across all grades of pain, relieving medicines than to ch was extrapolated to €5.34 billion or 2.86%isofoften Irish preventative medicines. This situation 7 seen withdemonstrates reliever and preventer in cost P per year. This an urgentinhalers need for respiratory disease.chronic Adherence also be ctive strategies to manage painmay effectively.
affected by patient co-morbidities for instance depressive illness is a strong predictor of nonadherence to medicines derstanding chronic painfor depression and other co-morbidities.2
onic pain is defined as pain that outlasts normal healing (iv) Therapy related factors e (usually three to six months), and is most frequently ociated with musculoskeletal disorders such as lowand A number of factors related to the medicine medication may affect patient k pain and arthritis. regimen However,itself it can also be associated adherence. These include frequency of doses h other disorders such as depression or metabolic (with an increase in non-adherence seen with orders orincreasing neurologicnumber conditions such as multiple of daily doses); patient rosis. understanding of directions given, the patient’s ability to use a delivery device such as inhaler,
insulin pen or transdermal patch,astaste of the n (acute or chronic) can be categorised nociceptive formulation and experience of side effects. europathic. Nociceptive pain is caused by an active ss, injury(v)and/or inflammatory process associated with Patient factors ual or potential tissue damage i.e. Nociceptive pain Patient beliefs about medicines have ults from been activity in neural pathways secondary to actual shown to be strongly associated 5 otential with tissue damage. Nociceptive pain isabout mediated adherence behaviour. Beliefs medicines are mediated by patient attitude and pain receptors located in skin, musculoskeletal system, knowledge of their condition and medication 8 e, and joints. Neuropathic pain, on the other hand, and counselling can be beneficial here. Patient ults from forgetfulness direct injury to peripheral or central sensory is aanother important factor and ve; the affected do notassociated produce transduction at may be nerves age-related, with the patient 8 placing importanceand on therapy or can occur iceptors.not Pain characteristics associated conditions in patients who do not have a regular daily both types of pain are shown in Table 1.
routine. According to one study, at least 1 in 7 Irish patients may have limited health literacy and this may affect their ability to manage their health.6 Therefore, limited health literacy may impact on patients’ ability to adhere to a medication regimen,
Self-report is a quick, convenient means of establishing non-adherence.2 It is useful in a clinical setting however it relies on patient cooperation as it can be manipulated and patients may give a socially-correct answer rather than admitting to a healthcare provider that they are not following advice.2 Several methods of self-report adherence assessment have been reported. These include informal clinician questioning and validated questionnaires.2 Validated questionnaires include the Morisky Medication Adherence Scale,7 the Medication Adherence Self-Report Inventory (MASRI)8 and the Brief Medication Questionnaire.9 TABLE 1. THE MORISKY MEDICATION ADHERENCE SCALE.7 1. Do you ever forget to take your medicine?
PATIENT CHARACTERISTICS PREDICTIVE OF NON-ADHERENCE
2. Are you careless at times about taking your medicine?
Major predictors of poor adherence to medication
3. When you feel better do you sometimes stop taking your medicine?
Presence of cognitive impairment
4. Sometimes if you feel worse when you take the medicine, do you stop taking it?
Treatment of asymptomatic disease
MEDICATION POSSESSION RATIO
Inadequate follow-up or discharge planning
Complexity of treatment
Refill adherence or medication possession ratio (MPR) is a calculation to establish the percentage of time a patient has a medication available to them. An MPR provides a view of the patient’s adherence over an extended period of time and is particularly useful in identifying non-persistence – that is the complete discontinuation of a medication. A refill adherence rate of 80% or 85% is the usual cut-off value for a patient to be considered adherent. While MPR is objective and easily calculated it is not the equivalent of assessing if the patient has ingested the medicine.2
Cost of medication, copayment or both
SIMPLE MPR CALCULATION:
Adapted from Osterberg and Blaschke, 20052
[ (Number of doses dispensed / number of doses required) * 100 ]
Presence of psychological problems, particularly depression
Side effects of medication Patient’s lack of belief in benefit of treatment Patient’s lack of insight into the illness Poor provider-patient relationship Presence of barriers to care or medications Missed appointments
MEASURING NON-ADHERENCE A major challenge in monitoring medication
The effect of non-adherence on patient outcomes
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CPD 40: MEDICATION ADHERENCE IN CHRONIC DISEASE
Adherence to and persistence with medication taking has been shown to be associated with improved outcomes for patients in asymptomatic and symptomatic disease.10,11 ASYMPTOMATIC DISEASE In an Irish primary care population, adherence to statin therapy has been shown to positively impact on low-density lipoprotein (LDL)Educational distance cholesterol levels.10 Patients were taking part in a cardiovascular screening study and adherence was assessed using the 4-item Morisky Medication Adherence Scale. Overall, just 51% of patients reported full adherence on the questionnaire and patients who achieved their goal LDL-cholesterol level were significantly more likely to report adherence (59.2% of LDL-cholesterol goal achievers vs. 39.6% of LDL-cholesterol goal non-achievers). Patients who reported nonadherence were twice as likely as adherent patients to fail to reach LDL-cholesterol goal. In this study, positive beliefs about medicines were also shown to be strongly associated with medication adherence.
heart failure followed up for on average 3 years, a comprehensive pharmacy care programme on adherence, blood pressure levels and 53 (29%) patients were identified as being nonLDL-cholesterol levels in elderly patients with persistent with at least one prescribed heart polypharmacy.13 For the first 6 months, all failure medicine (ACE inhibitor, angiotensin patients received education, regular pharmacist receptor blocker, beta-blocker or aldosterone Module 1 follow-up and blister packed medications. At antagonist).11 There was no medical reason for June 2012the this point, adherence was 97% across discontinuing the medicine in 50% of the nongroup. For the next 6 months patients were persistent cases. In this study, non-persistent randomised to continuing the intervention patients were at three-times increased risk orinreturning of rehospitalisation for healthcare any cause and fourlearning content for professionals Irelandto usual care. At 12 months, intervention patients were significantly more times increased risk of hospitalisation for likely to be adherent than usual care patients cardiovascular causes compared to patients (96% vs. 69% adherent). Medication adherence who had persisted with their prescribed heart was associated with a significant reduction in failure therapies. systolic blood pressure but not with a reduction in LDL-cholesterol. The results demonstrate that ADHERENCE INTERVENTIONS the intervention needs to be sustained in order A large review of adherence interventions to impact on adherence and clinical outcome. reported that successful interventions need to be long-term and complex.12 The interventions Another American study randomised heart reported on consisted of combinations failure patients to usual care or an intervention provided by a trained pharmacist. The of 2 or more of the following: improving pharmacist used a protocol to provide verbal convenience of care; providing information; and written instructions to patients regarding providing reminders; patient self-monitoring; their medicines, applied specially developed reinforcement of information; counselling for labels to heart failure medicines and provided patient or family counselling; psychological a drug calendar.14 Intervention patients had therapy; telephone follow-up and supportive significantly better adherence, measured by care. electronic medication monitoring, at nine-month follow-up compared with usual care patients An American study has examined the effect of
Chronic Pain – assessment and management in primary care
SYMPTOMATIC DISEASE In an Irish study of 183 patients with systolic
Introduction Pain is one of the commonest reasons for patients to seek medical attention.1 A recent survey has shown that as many as 8.3 visits per year to primary care physicians in Ireland were due to symptoms of pain.2 A large scale survey carried out in 15 European countries and Israel in 2006, screening 46,394 respondents reported that the prevalence of chronic pain of moderate to severe intensity in adult Europeans was 19%.3 More recent survey data from another study, carried out in 2,019 people with chronic pain and 1,472 primary care physicians across 15 European countries, have demonstrated that chronic pain affects 12-54% of adult Europeans, and its prevalence in Ireland is up to 13%.2 The PRIME (Prevalence, Impact and Cost of Chronic Pain) study, on the other hand, determined the prevalence of chronic pain to be as high as 35.5% in Ireland.4 The PRIME study was designed to investigate the prevalence of chronic pain in Ireland; compare the psychological and physical health profiles of those with and without chronic pain; and explore pain-related disability.4 Responses to survey questions were obtained from 1,204 people. Despite the magnitude of the problem, chronic pain is both under-recognised and undertreated in primary care.2,5 Indeed, up to 38% of patients reported being inadequately managed in primary care for their pain symptoms.2 In addition, people with chronic pain reported waiting up to 2.2 years between seeking help and diagnosis, and 1.9 years before their pain was adequately managed.2 Pharmacists are key in helping patients improve adherence
use by Healthcare Professionals in the Republic of Ireland only Learning, Evaluation,For Accredited, Readers, Network | www.learninpharmacy.ie © Copyright 2012 Pfizer Healthcare Ireland Date of Preparation: Module 1 June 2012 EPBU/2012/XXX
Sheehan et al reported in 1996 that the estimated cost of pain for 95 patients to the Irish Health Services when added to the amount of Social Welfare payments received and the lost earnings of each patient amounted to 1.9 million pounds at the time of referral.6 The recent data from PRIME survey show that the mean cost per chronic pain patient is estimated at €5,665 per year across all grades of pain, which was extrapolated to €5.34 billion or 2.86% of Irish GDP per year.7 This demonstrates an urgent need for cost effective strategies to manage chronic pain effectively.
Understanding chronic pain Chronic pain is defined as pain that outlasts normal healing time (usually three to six months), and is most frequently associated with musculoskeletal disorders such as low back pain and arthritis. However, it can also be associated with other disorders such as depression or metabolic disorders or neurologic conditions such as multiple sclerosis. Pain (acute or chronic) can be categorised as nociceptive or neuropathic. Nociceptive pain is caused by an active illness, injury and/or inflammatory process associated with actual or potential tissue damage i.e. Nociceptive pain results from activity in neural pathways secondary to actual or potential tissue damage. Nociceptive pain is mediated by pain receptors located in skin, musculoskeletal system, bone, and joints.8 Neuropathic pain, on the other hand, results from direct injury to a peripheral or central sensory nerve; the affected nerves do not produce transduction at nociceptors.8 Pain characteristics and associated conditions for both types of pain are shown in Table 1.
CPD 40: MEDICATION ADHERENCE IN CHRONIC DISEASE adherence and barriers to adherence. Patient Educ Couns. 1999;37:113-124. (10)
Bermingham M, Hayden J, Dawkins I et al. Prospective analysis of LDL-C goal achievement and self-reported medication adherence among statin users in primary care. Clin Ther. 2011;33:1180-1189.
Mockler M, O’Loughlin C, Murphy N et al. Causes and consequences of nonpersistence with heart failure medication. Am J Cardiol. 2009;103:834838.
Haynes RB, Ackloo E, Sahota N, McDonald HP, Yao X. Interventions for enhancing medication adherence. Cochrane Database Syst Rev. 2008;2:CD000011.
Lee JK, Grace KA, Taylor AJ. Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: a randomized controlled trial. JAMA. 2006;296:2563-2571.
Murray MD, Young J, Hoke S et al. Pharmacist intervention to improve medication adherence in heart failure: a randomized trial. Ann Intern Med. 2007;146:714-725.
Sahm L, MacCurtain A, Hayden J, Roche C, Richards HL. Electronic reminders to improve medication adherence--are they acceptable to the patient? Pharm World Sci. 2009;31:627-629.
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(79% vs. 68% adherence). However the effect of the intervention did not sustain and three months after the intervention ceased there was no significant difference in adherence between groups (71% vs. 67% adherence), again ehan et demonstrating al reported in 1996 that for thethe estimated costtoof the need intervention be long-term. was a 19% lower rate added of n for 95 patients to theThere Irish Health Services when heart failure exacerbations requiring hospital he amount of Social Welfare payments received and admission or emergency department visits lost earnings of each patient amounted to 1.9 million among intervention patients compared with 6 nds at the time of referral. The recent dataPatients from PRIME usual care during the study period. vey showinthat mean cost peralso chronic pain patient the the intervention group reported greater in year quality of lifeall over the follow-up stimatedimprovement at €5,665 per across grades of pain, period compared to usual care patients.
ch was extrapolated to €5.34 billion or 2.86% of Irish 7 P per year. This demonstrates an urgent for cost EVERYDAY INTERVENTIONS TOneed IMPROVE ADHERENCE ctive strategies to manage chronic pain effectively.
Sabate E. Adherence to long-term therapies: evidence for action. World Health Organisation. 2003.
Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487497.
Cramer JA, Roy A, Burrell A et al. Medication compliance and persistence: terminology and definitions. Value Health. 2008;11:44-47.
Viswanathan M, Golin CE, Jones CD et al. Interventions to improve adherence to self-administered medications for chronic diseases in the United States: a systematic review. Ann Intern Med. 2012;157:785-795.
Gatti ME, Jacobson KL, Gazmararian JA, Schmotzer B, Kripalani S. Relationships between beliefs about medications and adherence. Am J Health Syst Pharm. 2009;66:657-664.
Sahm LJ, Wolf MS, Curtis LM, McCarthy S. Prevalence of limited health literacy among Irish adults. J Health Commun. 2012;17 Suppl 3:100-108.
Practical solutions may be offered to patients
who have difficulty pain adhering to medication. derstanding chronic
Dispensing medicines in a pill organiser onic pain(“dosette is defined as pain that outlasts normal healing box”) or blister packaging may help patients who forget to take their medicines e (usually three to six months), and is most frequently or forget what time they should take their ociated with musculoskeletal disorders such as low medicines. This may be especially helpful where k pain and arthritis. However, it can or also be associated the patient has many doses a large number h other disorders suchtoastake depression or metabolic of medicines throughout the day.
orders or neurologic conditions such as multiple Setting alarms and reminders (such as on a rosis.
mobile phone) may help patients to remember (7) Morisky DE, Green LW, Levine DM. to take medicines. Although patients or their Concurrent and predictive validity of a n (acute or chronic) can be categorised as nociceptive carers can set this up themselves, several self-reported measure of medication europathic. Nociceptive pain is caused by an active websites provide services that will send a adherence. Med Care. 1986;24:67-74. message reminderprocess to patients and morewith ss, injurytext and/or inflammatory associated recentlytissue medicines management mobilepain (8) Walsh JC, Mandalia S, Gazzard BG. ual or potential damage i.e. Nociceptive phone applications have been available. Responses to a 1 month self-report ults from Among activity patients in neuralattending pathwaysansecondary to actual on adherence to antiretroviral therapy Irish community otential pharmacy tissue damage. Nociceptive unintentional pain is mediated are consistent with electronic data and who self-reported virological treatment outcome. AIDS. non-adherence antidepressant medication, pain receptors located intoskin, musculoskeletal system, 2002;16:269-277. 8reported that text message adherence 60% e, and joints. Neuropathic pain, on the other hand, reminders were acceptable to them.15 Therefore, ults from direct injury to a peripheral or central sensory (9) Svarstad BL, Chewning BA, Sleath simple, practical and inexpensive solutions exist BL, Claesson C. The Brief Medication ve; the affected nerves do not amongst produce transduction to improve adherence patients who at Questionnaire: a tool for screening patient 8 iceptors.arePain characteristics and associated conditions unintentionally non-adherent.
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both types of pain are shown in Table 1.
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