Faculty of Pharmacy, World University of Bangladesh
Dhanmondi, Dhaka, Bangladesh

The word ‘compliance’ comes from the Latin word complire, meaning to fill up and hence to complete an action, transaction, or process and to fulfil a promise. In the Oxford English Dictionary, the relevant definition is ‘The acting in accordance with, or the yielding to a desire, request, condition, direction, etc.; a consenting to act in conformity with; an acceding to; practical assent”. Compliance with therapy is simply patients understanding of medication, motivation toward having this medication is a prescribed manner with the belief that the prescriber and prescribed medicine will be beneficial for his well-being. Although this is often the case, in a number of situations, the physician and pharmacist have not provided the patient with adequate instructions or have not presented the instructions in such a manner that the patient understands them. Nothing should be taken for granted regarding the patient’s understanding of how to use medication, and appropriate steps must be taken to provide patients with the information and counseling necessary to use their medications as effectively and as safely as possible. 20% to 30% of new prescriptions are never filled at the pharmacy. Medication is not taken as prescribed 50% of the time. For patients prescribed medications for chronic diseases, after six months, the majority take less medication than prescribed or stop the medication altogether. There are both federal and state laws that make using or sharing prescription drugs illegal. If someone take a pill that was prescribed to someone else or give that pill to another person, not only is it against the law, it's extremely dangerous.

Reference Id: PHARMATUTOR-ART-2641

According to the WHO, lack of adherence to medical treatment regimen gives rise to major clinical problems in patients, mostly with chronic illness. Rates of nonadherence with any medication treatment varies from 15% to 93%, with an average estimated rate of 50% worldwide. “Drugs don’t work if people don’t take them.” This observation made by former Surgeon General C Everett Koop in his keynote address at a symposium on Improving Medication Compliance, provides a clear statement of one of the consequences of noncompliance. In many cases noncompliance results in underuse of a drug, thereby depriving the patient of the anticipated therapeutic benefits and possibly resulting in a progressive Medication nonadherence for patients with chronic diseases is extremely common, affecting as many as 40% to 50% of patients who are prescribed medications for management of chronic conditions such as diabetes or hypertension. This nonadherence to prescribed treatment is thought to cause at least 100,000 preventable deaths and $100 billion in preventable medical costs per year. Despite this, the medical profession largely ignores medication nonadherence or sees it as a patient problem and not a physician or health system problem. A recent BMJ study shows annual costings of medication non-adherence range from USD 100 to USD 290 billion in USA, €1.25 billion in Europe and approximately $A7 billion in Australia. Along with staggering economic losses, patient compliance also presents a major hurdle to patient health. For instance, compliance rates below 90% for HIV patients can cause viral replication and disease progression while for diabetics, proper compliance is essential in preventing hypertension and myocardial infarction. Adherence consists of 3 essential factors:
A. Patient: Takes treatment decision process by their own, based on individual literacy and feedback from others, mostly non-professionals.
B. Provider: Prescribe drug/non-drug treatments and face communication barriers
C. Healthcare system: access to care, time allotted for technical support

Types of patients: Based on the acceptance of diagnosis and treatment initiation, patients are categorized into four types
• Non-compliers: Those who do not accept both diagnosis and need treatment.
• Partial compliers: Those who accept diagnosis and treatment but fulfill the recommended actions partially, occasionally and sometimes never.
• Over compliers: These patients are rare.
• Adequate compliers: Those who follow treatment advise adequately to improve or control their disorder (Manmohan, 2012)

Types of Medication Taking Behavior
a. Compliance: Understanding providers instructions consciously and behavior coincides with medical & health advice, also applicable for other situations such as medical device use, self-care, self-directed exercises, or therapy sessions. Given a specific prescription, compliance can be further classified with respect to the potential ways a patient can deviate from a provider’s instructions. Primary compliance is defined as a patient’s fidelity of filling and refilling prescriptions. Secondary compliance refers to whether a patient actually consumes their medication.
b. Adherence: WHO defines adherence as “The extent to which a person’s behavior, corresponds with agreed recommendations from a health care professional”. Adherence is broadly related to instructions concerning medicine intake, use of medical device, diet, exercise, life style changes, rest and return for scheduled appointments.
c. Concordance: Consultative and consensual therapy partnership between the consumer and their doctor. Concordance is when a patient and clinician make decisions together about treatment.
d. Persistence: A person’s ability to continue medical advice that may range from few days to life-long (Fraser, 2010 and Klobusicky, 2017).

Dimensions of Patient Medication Adherence
Adherence is a multidimensional phenomenon determined by the interaction of five sets of factors - termed "dimensions" by the WHO. These dimensions are: 
• Social/economic: It’s a social support from acquaintance or caregivers to assist with medication regimens have better adherence to treatment. People with poor healthcare access, unstable living, financial lack, high medication costs are of decreased adherence rates. 
• Provider-patient/health care system: A good provider patient relationship, reinforce and motivates patients to adhere treatment regimens. Conversely, Poor or lack of communication contributes nonadherence, especially in older adults with cognitive dysfunction.
• Condition-related: In chronic illness, where drug administration is lengthy, adherence significantly declines over time, its human nature. Mostly happens when symptoms are not prominent, diminished or absent.
• Therapy-related: The complexity of the medication regimen, numbers of medications and their daily doses, long-term therapy recommended that interferes patient’s lifestyle or the untoward effects that discomfort patients results non-adherence.
• Patient factors: Physical impairments and cognitive dysfunctions may increase the risk for nonadherence in older adults. Poor knowledge about the disease and the reasons why medication is needed, lack of motivation, low self-efficacy, and substance abuse are associated with poor medication adherence (Fatima, 2018, Wu, 2008, Sabate, 2003).

Medication Non-adherence: An Eccentric East West Analogy
Medication nonadherence remains a substantial public health problem. Causes of medication non-adherence are complex and include psychosocial (eg, alcohol use, depression, stigma), structural (eg, distance from clinics, medication costs), therapy-related (eg, toxicities) and health system–related barriers (eg, lack of counselling, poor user-experience with the health system) (Subbaraman, 2018). Studies have found that patients’ beliefs about medicines and their perception of their illness contribute towards poor adherence (Kumar, 2016). Worldwide, between 25% and 50% of patients do not take their medications as recommended. In the USA, suboptimal adherence has been associated with 125,000 deaths, 10% of hospitalizations, and costs 300 billion USD annually (Zullig, 2018). The economic impact was also in PubMed and Scopus in September 2017, which shows an increase in total healthcare cost (>80%), pharmacy costs (70%), inpatient and outpatient costs (50%), emergency department visit and medication costs (<30%), and hospitalization costs (<20%) (Cutler, 2018). Nearly 70% of all medication-related hospital admissions are due to medication non-adherence alone (Kuo, 2016). Across South Asia, overall hypertension prevalence is estimated to be 27%. Prospective Urban Rural Epidemiology study has shown more than 50% are unaware of it and up to 80% of hypertensive patients have low adherence to medication (Naheed, 2018). Uncontrolled BP was found more than 50% in Bangladesh, 70% in Pakistan and almost 60% in Sri Lanka (Jafar, 2018). American Diabetes Association and the European Association for the Study of Diabetes guidelines in 10 developing countries from Africa (Egypt, South Africa), Middle East (Israel, Saudi Arabia, United Arab Emirates, Iran and Lebanon) and South Asia (Bangladesh, India and Pakistan) shows more than 25% and around 70% patients did not have any follow-up visit by a diabetologist or a GP, respectively. More than 35% patients did not receive any diabetes education (Al-Mansari, 2018). In a study conducted among people with diabetes only 30% were compliant with drug regimens and the non-compliance was higher among the lower socioeconomic groups (Shrivastava, 2013).

Non-patient Factors associated with Non-adherence
• The nature of patient illness
• Therapeutic regime
• Treatment duration
• Frequency of drug administration
• Adverse events
• Taste of medication

Patient Non-Compliance
Non-compliance with drug treatment is widespread. When patients are given medication by their doctors, nearly half do not take the drug or do not take it as prescribed, and most will stop the treatment as soon as they are feeling better. A major problem in identifying the non-compliant patient is the unreliability of many of the measures used for assessing compliance. There are few social and demographic characteristics associated with non-compliance. The type of disease, also, generally has little influence on the level of compliance. Psychological factors such as the patients' levels of anxiety, motivation to recover, attitudes towards their illness, the drug and the doctor, as well as the attitudes and beliefs of significant others in their environment do influence the patients' levels of compliance (Evans, 1983). One of the more compelling rationales offered for expanding drug coverage is that affordability problems have clinical as well as economic consequences; that is, patients who have difficulty paying for medications are less likely to take them and can suffer adverse health effects as a result of noncompliance (Kennedy, 2002).

Types of Non-compliance
The situations most commonly associated with noncompliance with drug therapy include following situations:
a) Some patients for whom medication has been prescribed do not even take their prescriptions to a pharmacy, and some others who do take their prescriptions to a pharmacy fail to pick them up when they are completed.
b) The omission of doses is one of the most common types of noncompliance and occurs when a medication is to be administered at frequent intervals and/or for an extended period of time.
c) Errors of dosage include situations when incorrect amount of an individual dose or frequency of administration occurs
d) Examples of the incorrect administration of medication include not using the proper technique in using metered-dose inhalers and, in some cases, giving medication by the wrong route of administration.
e) Errors in the time of administration of the drug may include situations in which medication is administered in an inappropriate relationship to meals. Certain drugs—e.g., tetracycline, alendronate (Fosamax)—should be administered apart from meals to achieve optimal absorption. The time of day at which a drug is administered also may be important in the use of some medications; e.g., diuretics are best administered in the morning.
f) The premature discontinuation of treatment occurs commonly with the use of antibiotics as well as medications used in the treatment of chronic disorders such as hypertension (Hussar, 2006).

Reasons of Non-compliance in elderly patients
Currently the aging population is rapidly increasing, particularly in developing regions of the world, due to longer expectancy of life, better healthcare facilities and greater awareness about healthy lifestyle. Today, in developed countries, more than 75% die after the age of 75 years (Lunenfeld, 2013).  Because of the progressively increasing geriatric population requiring special care, there is a growing global concern to improve the health care delivery systems, particularly against chronic and recurrent illnesses that occur more commonly during later life such as: diabetes mellitus, hypertension, IHD, arthritic disorders, neurodegenerative disorders, psychiatric illnesses, gastrointestinal disorders, ocular disorders, genitourinary disorders, respiratory disorders etc., which may require chronic medication with multiple drugs. Because of the chronic nature of the disease, the need for multiple drug therapy with complex medication regime, increasing cost of therapy, adverse effects, drug interactions, forgetfulness, lack of familial and social support and care, elderly patients may not be fully compliant to long term medications. In general, only 50% of general population has been estimated to adhere to their medications, and this may range from 47 to 100% in elderly. Poor compliance among older persons is a public health concern, as it accounts for adverse outcomes, medication wastage with increased cost of healthcare, and substantial worsening of the disease with increased disability or death (Shruthi, 2016). However, Notable Reasons behind elderly non-compliance issues are:

• Adverse effects
• Increased, or decreased sensitivity to drugs
• Frequent change of prescriptions (prescription cascade)
• Living alone
• Lack of social support system
• Difficulty in opening the medication container that has flip off type of lid
• Going to pharmacist/chemist due to physical problems like (osteoarthritis)
• Cognitive impairment
• Impaired mobility or dexterity
• Swallowing problems
• Financial issues like, Low income and high cost of medications
• Everyday inconvenience in carrying and taking of medicines (Jin, 2016)

Consequences of Non-compliance
Physicians frequently do not effectively communicate to their patients about the basic information of treatment plans. Patients may be left with concerns about adverse effects and with lack of comprehension of disease and treatment that adversely affect their adherence. Framing the problem of poor adherence on patients’ fear of side effects or lack of understanding does not clearly emphasize the physician’s responsibility to appropriately address these concerns. The same hurdle can be reformulated as a problem of physicians’ inadequate, ineffective communication to patients of critical information. This reformulation demonstrates that physicians have a responsibility to minimize barriers to non-compliance by changing that which physicians have control over patients’ own behavior (Devine, 2018). Notable non-compliance results are:
a) Underuse of a drug, deprives the patient of the anticipated therapeutic benefits and possibly resulting in a progressive worsening or other complications of the condition being treated e.g. underutilization and nonadherence of warfarin among nonvalvular AF patients is both prevalent and costly (Casciano, 2013). The statins significantly reduce morbidity and mortality in patients with CHD and in patients with hyperlipidemia, when they are used on a continuing basis (Rosuvastatin, up to 55% reduction in LDL, up to 20% lowering in triglycerides, and up to 10% increase in HDL) (Lardizabal, 2010). Underuse of antihypertensive medications may be associated with hospitalization that could have been prevented if patients had complied with their treatment regimens.

b) Overuse of a drug, mostly increases risk of ADR e.g. MOH reported with antimigraine drugs (ergots and triptans) including nausea, dizziness and coronary vasoconstriction (González-Hernández, 2018). AIM survey noted that 25% of patients rely on SABA monotherapy to manage their persistent asthma, many of whom use albuterol daily. MEPS noted that 15% of patients with asthma use more than 1 canister of albuterol per month. These patients had twice the risk of an asthma-related emergency department visit or hospitalization as compared to those who filled albuterol less frequently (Gerald, 2015)

Factors Associated with Non-compliance
Disease: Antipsychotic medication reduces the severity of serious mental illness (SMI), nonadherence to the treatment of SMI increases the risk of relapse and hospitalization. Poor insight was identified as a reason for nonadherence in more than 50% of studies, followed by a negative attitude toward medication in 30% and cognitive impairments in nearly 15% (Velligan, 2017). Patients with chronic disorders, particularly conditions such as hypertension (45% in Bengaluru, 50% in Pakistan and 60% in Mumbai) (Shah, 2018) and hypercholesterolemia (60% in Kuwait) (Al-Foraih, 2016), which often are not associated with symptoms are also more likely to be noncompliers. Patients understandably tend to become discouraged with extended therapeutic programs that do not produce cures of the conditions.



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