Adherence (medicine)(Redirected from Missed dose)
In medicine, compliance (also adherence, capacitance) describes the degree to which a patient correctly follows medical advice. Most commonly, it refers to medication or drug compliance, but it can also apply to other situations such as medical device use, self care, self-directed exercises, or therapy sessions. Both patient and health-care provider affect compliance, and a positive physician-patient relationship is the most important factor in improving compliance, The cost of prescription medication also plays a major role. Compliance rates may be overestimated in the medical literature, as compliance is often high in the setting of a formal clinical trial but drops off in a "real-world" setting.
Compliance can be confused with concordance, which is the process by which a patient and clinician make decisions together about treatment.
Worldwide, non-compliance is a major obstacle to the effective delivery of health care. 2003 estimates from the World Health Organization indicated that only about 50% of patients with chronic diseases living in developed countries follow treatment recommendations with particularly low rates of adherence to therapies for asthma, diabetes, and hypertension. Major barriers to compliance are thought to include the complexity of modern medication regimens, poor "health literacy" and not understanding treatment benefits, occurrence of undiscussed side effects, poor treatment satisfaction, cost of prescription medicine, and poor communication or lack of trust between a patient and his or her health-care provider. Efforts to improve compliance have been aimed at simplifying medication packaging, providing effective medication reminders, improving patient education, and limiting the number of medications prescribed simultaneously. Studies show a great variation in terms of characteristics and effects of interventions to improve medicine adherence. It is still unclear how adherence can consistently be improved in order to promote clinically important effects.
In medicine, compliance (synonymous with adherence, capacitance) describes the degree to which a patient correctly follows medical advice. Most commonly, it refers to medication or drug compliance, but it can also apply to medical device use, self care, self-directed exercises, or therapy sessions. Both patient and health-care provider affect compliance, and a positive physician-patient relationship is the most important factor in improving compliance,
As of 2003, US health care professionals more commonly used the term "adherence" to a regimen rather than "compliance", because it has been thought to reflect better the diverse reasons for patients not following treatment directions in part or in full. Additionally, the term adherence includes the ability of the patient to take medications as prescribed by their physician with regards to the correct drug, dose, route, timing, and frequency. It has been noted that compliance may only refer to passively following orders.
The term concordance has been used in the United Kingdom to involve a patient in the treatment process to improve compliance, and refers to a 2003 NHS initiative. In this context, the patient is informed about their condition and treatment options,involved in the decision as to which course of action to take, and partially responsible for monitoring and reporting back to the team. 
As of 2005, the preferred terminology remained a matter of debate. As of 2007, concordance has been used to refer specifically to patient adherence to a treatment regimen which the physician sets up collaboratively with the patient, to differentiate it from adherence to a physician-only prescribed treatment regimen.  Despite the ongoing debate, adherence has been the preferred term for the World Health Organization, The American Pharmacists Association, and the U.S. National Institutes of Health Adherence Research Network.
A WHO study estimates that only 50% of patients suffering from chronic diseases in developed countries follow treatment recommendations. The figures are even lower in respect to adherence rates for preventative therapies, and can be as low as 28% in developed countries. This may affect patient health, and affect the wider society when it causes complications from chronic diseases, formation of resistant infections, or untreated psychiatric illness.
Compliance rates during closely monitored studies are usually far higher than in later real-world situations. For example, a 2004 UK study reported a 97% compliance rate at the beginning of treatment with statins, but only about 50% of patients were still compliant after six months.
The experience of Patient Connect Service Limited in the UK is that medicines prescribed for preventative purposes are especially likely not to be taken as prescribed;[not in citation given] perhaps because people do not feel immediately threatened or, in the case of symptomless conditions such as raised cholesterol levels (hypercholesterolaemia) and raised blood pressure (systemic hypertension), feel no obvious benefits at the time of taking the medicines  As patients are asymptomatic, they may not see a need to take medication.
Figures from the UK on non-compliance:
- Up to 90% of diabetes patients do not take their medication well enough to benefit from that medication.
- 33-50% of some cancer patients take less of their anti-cancer medicine than required.
- only 75% of patients with coronary heart disease (CHD) take sufficient medicine for it to be effective.
- 70% of hypertensive patients do not adhere to their medicine.
- 41-59% of mentally ill patients took their medication infrequently or not at all in a 2003 review.
- 33% of patients with schizophrenia don’t take their medicine at all, and 33% were poorly adherent in a 2000 study.
- Less than 27% of depressed patients adhered to their medication in 2000.
In the UK, it has been estimated that if coronary heart disease patients adhered to their medication, each year 40,000 to 50,000 fewer people would have a stroke and 25,000 would not have a heart attack.
The financial cost to the UK National Health Service (NHS), and thus to British society, is high:
- coronary heart disease costs the NHS in excess of £2 billion on medicines; 50% of which is wasted through poor understanding and poor adherence.
- Economic studies consistently show that the costs incurred with poorly controlled asthma are higher than those for a well-controlled patient with the same severity of disease. For severe asthma, it has been estimated that the savings produced by optimal control would be around 45% of the total medical costs per the GINA Project (Global Initiative for Asthma) 2002.
An estimated half of those for whom treatment regimens are prescribed do not follow them as directed. Until recently,[when?] this was termed "non-compliance", which some regarded as meaning that someone did not follow the treatment directions due to irrational behavior or willful ignoring of instructions.
Cost and poor understanding of the directions for the treatment, referred to as 'health literacy' have been known to be major barriers to treatment adherence. There is robust evidence that education and physical health are correlated. Poor educational attainment is a key factor in the cycle of health inequalities.
Educational qualifications help to determine an individual’s position in the labour market, their level of income and therefore their access to resources.
In 1999 one fifth of UK adults, nearly seven million people, had problems with basic skills, especially functional literacy and functional numeracy, described as: "The ability to read, write and speak in English, and to use mathematics at a level necessary to function at work and in society in general." This made it impossible for them to effectively take medication, read labels, follow drug regimes, and find out more. This was
In 2003, 20% of adults adults in the UK had a long-standing illness or disability and a national study for the UK Department of Health, found more than one-third of people with poor or very poor health had literary skills of Entry Level 3 or below.
Low levels of literacy and numeracy were found to be associated with socio-economic deprivation. Adults in more deprived areas, such as the North East of England, performed at a lower level than those in less deprived areas such as the South East. Local authority tenants and those in poor health were particularly likely to lack basic skills.
A 2000 analysis of over 100 UK local education authority areas found educational attainment at 15–16 years of age to be strongly associated with coronary heart disease and subsequent infant mortality.
A study of the relationship of literacy to asthma knowledge revealed that 31% of asthma patients with a reading level of a ten-year-old knew they needed to see the doctors, even when they were not having an asthma attack, compared to 90% with a high school graduate reading level.
In 2013 the US National Community Pharmacists Association sampled for one month 1,020 Americans above age 40 for with an ongoing prescription to take medication for a chronic condition and gave a grade C+ on adherence.[better source needed] In 2009, this contributed to an estimated cost of $290 Billion annually. In 2012, increase in patient medication cost share was found to be associated with low adherence to medication.
The United States is among the countries with the highest prices of prescription drugs mainly attributed to the government's lack of negotiating lower prices with monopolies in the pharmaceutical industry especially with brand name drugs. In order to manage medication costs, many US patients on long term therapies fail to fill their prescription, skip or reduce doses. According to a Kaiser Family Foundation survey in 2015, about three quarters (73%) of the public think drug prices are unreasonable and blame pharmaceutical companies for setting prices so high. In the same report, half of the public reported that they are taking prescription drugs and a “quarter (25%) of those currently taking prescription medicine report they or a family member have not filled a prescription in the past 12 months due to cost, and 18 percent report cutting pills in half or skipping doses”. In a 2009 comparison to Canada, only 8% of adults reported to have skipped their doses or not filling their prescriptions due to the cost of their prescribed medications.
Both young and elderly status have been associated with non-adherence.
The elderly often have multiple health conditions, and around half of all NHS medicines are prescribed for people over retirement age, despite representing only about 20% of the UK population. The recent National Service Framework on the care of older people highlighted the importance of taking and effectively managing medicines in this population. However, elderly individuals may face challenges, including multiple medications with frequent dosing, and potentially decreased dexterity or cognitive functioning. Patient knowledge is a concern that has been observed.
In 1999 Cline et al. identified several gaps in knowledge about medication in elderly patients discharged from hospital. Despite receiving written and verbal information, 27% of older people discharged after heart failure were classed as non-adherent within 30 days. Half the patients surveyed could not recall the dose of their medication and nearly two-thirds did not know what time of day to take them. A 2001 study by Barat et al. evaluated the medical knowledge and factors of adherence in a population of 75-year-olds living at home. They found that 40% of elderly patients do not know the purpose of their regimen and only 20% knew the consequences of non-adherence. Comprehension, polypharmacy, living arrangement, multiple doctors, and use of compliance aids was correlated with adherence. According to a conservative estimate 10% of all hospital admissions[where?] are through patients not managing their medication.
In children with asthma self-management compliance is critical and co-morbidites have been noted to affect outcomes; in 2013 it has been suggested that electronic monitoring may help adherence.
Social factors of treatment adherence have been studied in children and adolescent psychiatric disorders:
- Young people who felt supported by their family and doctor, and had good motivation, were more likely to comply.
- Young adults may stop taking their medication in order to fit in with their friends, or because they lack insight of their illness.
- Those who did not feel their condition to be a threat to their social well-being were eight times more likely to comply than those who perceived it as such a threat.
- Non-adherence is often encountered among children and young adults; young males are relatively poor at adherence.
People of different ethnic backgrounds have unique adherence issues through literacy, physiology, culture or poverty. There are few published studies on adherence in medicine taking in ethnic minority communities. Ethnicity and culture influence some health-determining behaviour, such as participation in screening programmes and attendance at follow-up appointments.
Prieto et al emphasised the influence of ethnic and cultural factors on adherence. They pointed out that groups differ in their attitudes, values and beliefs about health and illness. This view could affect adherence, particularly with preventive treatments and medication for asymptomatic conditions. Additionally, some cultures fatalistically attribute their good or poor health to their god(s), and attach less importance to self-care than others. also
Measures of adherence may need to be modified for different ethnic or cultural groups. In some cases, it may be advisable to assess patients from a cultural perspective before making decisions about their individual treatment.
Prescription fill ratesEdit
Not all patients will fill the prescription at a pharmacy. In a 2010 U.S. study, 20-30% of prescriptions were never filled at the pharmacy. Reasons people do not fill prescriptions include the cost of the medication, A US nationwide survey of 1,010 adults in 2001 found that 22% chose not to fill prescriptions because of the price, which is similar to the 20-30% overall rate of unfilled prescriptions. Other factors are doubting the need for medication, or preference for self-care measures other than medication. Convenience, side effects and lack of demonstrated benefit are also factors.
Medication Possession RatioEdit
Prescription medical claims records can be used to estimate medication adherence based on fill rate. Patients can be routinely defined as being 'Adherent Patients' if the amount of medication furnished is at least 80% based on days supply of medication divided by the number of days patient should be consuming the medication. This percentage is called the medication possession ratio (MPR). 2013 work has suggested that a medication possession ratio of 90% or above may be a better threshold for deeming consumption as 'Adherent'.
Two forms of MPR can be calculated, fixed and variable. Calculating either is relatively straightforward, for Variable MPR (VMPR) it is calculated as the number of days supply divided by the number of elapsed days including the last prescription.
For the Fixed MPR (FMPR) the calculation is similar but the denominator is the number of days in a year whilst the numerator is constrained to be the number of days supply within the year that the patient has been prescribed.
For medication in tablet form it is relatively straightforward to calculate the number of days supply based on a prescription. Some medications are less straightforward though because a prescription of a given number of doses may have a variable number of days supply because the number of doses to be taken per-day varies, for example with preventative corticosteroid inhalers prescribed for asthma where the number of inhalations to be taken daily may vary between individuals based on the severity of the disease.
Once started, patients seldom follow treatment regimens as directed, and seldom complete the course of treatment. In respect of hypertension, 50% of patients completely drop out of care within a year of diagnosis. Persistence with first-line single antihypertensive drugs is extremely low during the first year of treatment. As far as lipid-lowering treatment is concerned, only one third of patients are compliant with at least 90% of their treatment. Intensification of patient care interventions (e.g. electronic reminders, pharmacist-led interventions, healthcare professional education of patients) improves patient adherence rates to lipid-lowering medicines, as well as total cholesterol and LDL-cholesterol levels.
The World Health Organization (WHO) estimated in 2003 that only 50% of people complete long-term therapy for chronic illnesses as they were prescribed, which puts patient health at risk. For example, in 2002 statin compliance dropped to between 25-40% after two years of treatment, with patients taking statins for what they perceive to be preventative reasons being unusually poor compliers.
A wide variety of packaging approaches have been proposed to help patients complete prescribed treatments. These approaches include formats that increase the ease of remembering the dosage regimen as well as different labels for increasing patient understanding of directions. For example, medications are sometimes packed with reminder systems for the day and/or time of the week to take the medicine. Some evidence shows that reminder packaging may improve clinical outcomes such as blood pressure.
A not-for-profit organization called the Healthcare Compliance Packaging Council of Europe] (HCPC-Europe) was set up[when?] between the pharmaceutical industry, the packaging industry with representatives of European patients organizations. The mission of HCPC-Europe is to assist and to educate the healthcare sector in the improvement of patient compliance through the use of packaging solutions. A variety of packaging solutions have been developed by this collaboration.
World Health Organization Barriers to AdherenceEdit
The World Health Organization (WHO) groups barriers to medication adherence into five categories; health care team and system-related factors, social and economic factors, condition-related factors, therapy-related factors, and patient-related factors. Common barriers include:
|Poor Patient-provider Relationship||Health Care Team and System|
|Inadequate Access to Health Services||Health Care Team and System|
|High Medication Cost||Social and Economic|
|Cultural Beliefs||Social and Economic|
|Level of Symptom Severity||Condition|
|Availability of Effective Treatments||Condition|
|Immediacy of Beneficial Effects||Therapy|
|Stigma Surrounding Disease||Patient|
|Inadequate Knowledge of Treatment||Patient|
Improving compliance ratesEdit
Compliance with treatment can be improved by:
- Selecting treatments in a way that minimizes side-effects, and discussing management of side effects
- Prescribing the minimum number of different medications
- Simplifying medication dosage regimen by selecting a drug or using a sustained release preparation that requires as few doses per day as possible
- Having open discussions around medication options, and alternatives if the first option is not toleratedPatients' adherence with their medication is poor across all chronic diseases, including coronary heart disease, mental health, diabetes and cancer. This poor adherence results in significant increase in illness, disability, symptoms and even death.
Careful choice of medication by the prescribing physician, along with the provision of greater information to the patient can improve compliance. For example, in a 2000 study patients taking typical antipsychotics tended to experience more severe side-effects, and also receive less information about their illness, medicines and side-effects. They were naturally more likely to be non-compliant than those receiving atypicals.
One tool for measuring patient medication compliance has been the proprietary Morisky Medication Adherence Scale, first developed in 1986. This test has come under fire due to its high cost to academic researchers, prompting a need for an open source adherence scale.
Role of health care providersEdit
Health care providers play a great role in improving adherence issues. Providers can improve patient interactions through motivational interviewing and active listening. Health care providers should work with patients to devise a plan that is meaningful for the patient’s needs. A relationship that offers trust, cooperation, and mutual responsibility can greatly improve the connection between provider and patient for a positive impact.Template:Full reference
As more patient cohorts become adept at using technology in their daily lives, it will become easier to integrate technology into patient care and compliance. There are[when?] multiple opportunities to use technology to boost patient compliance rates, and make it easier for patients to become involved in their own care. As part of the push to encourage implementation of electronic health records in hospitals and private practices, the US government has set "meaningful use" objectives and benchmarks, like the use of a patient portal, through which patients can securely view lab reports, request prescription refills, and ask questions of their providers - all of which can increase patient compliance with care plans.
Mobile technology like tablets, smartphones, and other devices can be equipped with any number of medical apps to help with patient monitoring and compliance. Text-message reminders are[when?] increasingly being used[where?] to help with patient compliance; A 2012 publication stated that daily text messages sent to remind patients to take their medication have improved compliance rates and patient health especially in younger patients with chronic illnesses such as diabetes, and young women who take contraceptives.
In 2012 it was predicted that as telemedicine technology improves, physicians will have better capabilities to remotely monitor patients in real-time and to communicate recommendations and medication adjustments using personal mobile devices, such as smartphones, rather than waiting until the next office visit.
Medication Event Monitoring Systems, as in the form of smart medicine bottle tops, smart pharmacy vials or smart blister packages as used in clinical trials and other applications where exact compliance data are required, work without any patient input, and record the time and date the bottle or vial was accessed, or the medication removed from a blister package. The data can be read via proprietary readers, or NFC enabled devices, such as smartphones or tablets. A 2009 study stated that such devices can help improve adherence.
A number of initiatives have involved "real time" adherence monitoring with differing definitions of "real time". A "talking pill" or one which can communicate its status on an ongoing real time basis is not feasible. In all cases, the medication taking event is represented in a system by proxy. For instance, the time a trace was broken on a package when a dose cavity was accessed. In this case there is no proof that the medication was a) removed or b) ingested. Proof of ingestion and the time staying of it is in and by itself a difficult task to accomplish. While sounding most useful and technically feasible, it has not been meeting with much success to-date. Even the most cutting-edge ingestion based product, Proteus' Helio, requires the ingestion of a non-active second dose enabled with a transmitting function which does not prove ingestion of the active dose at all. It is debatable how much acceptance this type of ingested sensor will have with the general public. At the moment,[when?] a prescription is required just to receive a sensor system.
In most parts of the world, medication is dispensed in blister packaging. It is relatively simple to equip blister packages with printed conductive trace grids. These grids are then connected to an electronic module. The electronic monitor records the time a trace has been broken and can then transmit this information to an NFC smart phone or even be GSM enabled to transmit the information immediately if a suitable data network is available. A more reasonable solution at the moment would be to connect the package to a hub, handheld device, tablet or smart watch via low power Bluetooth. In this case the package data would be sent whenever the medication blister is in close proximity to the bluetooth receiver. It avoids the huge effort required to equip every single blister with a SIM module and expensive monthly data subscription.
The question of real time is not solved by simply generating data which is based on a proxy of ingestion. If such data is not being parsed and used in an effective fashion to assist patients, caregivers and medical professionals with adherence management, then it is not a useful application of expensive resources. It can be argued that the highest and best use of technologies such as smart blister packages, are in stratifying patient groups into good compliers and poor compliers. In this case, the poor compliers maybe coached more intensively, and the good compliers have a continued incentive to remain adherent. Real time in this case might be achieved by sending a regular series of SMS, frequency depending on their adherence status, and requesting them to upload their NFC sensor data through their handheld or wrist worn device.
There appears to be as much confusion about smart adherence technology as there is whenever a new technology comes on stream. Overzealous journalists tend to confuse science fiction with reality. Marketers and PR departments over promise and engineering and product departments under deliver. In the end, if a fair balance isn't struck between a feasible cost effective solution and unrealistic expectations derived from over confident presentations, the entire field of smart adherence monitoring is in danger of being ignored.
For the time being, the most applicable field of endeavour for smart adherence management is in clinical trials. This is also where most of the existing devices are being used at the moment.
In the UK millions of patients are given information at the point of dispensing to help them better understand their medicines, with measurable impact on patient compliance.
In the UK, a literature service and its pharmacy partners have completed a 200,000 patient survey in 2013 into the effect of pharmacists providing to patients the information that patients want, which show that where a pharmacist talks through the leaflet given to the patient, there is an increase in adherence by between 16% and 33% within three months.[dead link][better source needed]
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Health and disease managementEdit
The failure to complete treatment regimens as prescribed has significant negative health impacts worldwide. Examples of the rate and consequences of non-compliance for selected medical disorders arte as follows:
Asthma non-compliance (28-70% worldwide) increases the risk of severe asthma attacks requiring preventable ER visits and hospitalizations.
Compliance issues with asthma can be caused by a variety of reasons including: difficult inhaler use, side effects of medications, and cost of the treatment.
Since Asthma is an ongoing disease and patients may go through periods where they do not have symptoms, this can interfere with proper use of steroid inhalers. Steroid inhalers need to be taken on a daily basis even if the patient is feeling well. The only time that it is allowable to stop taking a steroid inhaler is with a doctor's approval. To help manage adherence in asthma patients, the most important factors in improving compliance included patient education, motivational interviewing, and setting goals of therapy. Explaining the differences between the types of inhalers and telling patients that steroid inhalers will need to be taken every day can help to improve adherence in this population.
200,000 new cases of cancer are diagnosed each year in the UK. One in three adults in the UK will develop cancer that can be life-threatening, and 120,000 people will be killed by their cancer each year. This accounts for 25% of all deaths in the UK. However while 90% of cancer pain can be effectively treated, only 40% of patients adhere to their medicines due to poor understanding.
The reasons for non-adherence have been given by patients as follows:
- The poor quality of information available to them about their treatment.
- A lack of knowledge as to how to raise concerns whilst on medication.
- Concerns about unwanted effects.
- Issues about remembering to take medication.
Partridge et al (2002) identified evidence to show that adherence rates in cancer treatment are variable, and sometimes surprisingly poor. The following table is a summary of their findings:
|Type of Cancer||Measure of non-Adherence||Definition of non-Adherence||Rate of Non-Adherence|
|Haematological malignancies||Serum levels of drug metabolites||Serum levels below expected threshold||83%|
|Breast Cancer||Self-report||Taking less than 90% of prescribed medicine||47%|
|Leukemia or non Hodgkin's lymphoma||Level of drug metabolite in urine||Level lower than expected||33%|
|Leukemia, Hodgkin's disease, non Hodgkin's||Self-report and parent report||More than one missed dose per month||35%|
|Lymphoma, other malignancies||Serum bioassay||Not described|
|Hodgkin's disease, acute lymphocytic leukemia (ALL)||Biological markers||Level lower than expected||50%|
|ALL||Level of drug metabolite in urine||Level lower than expected||42%|
|ALL||Level of drug metabolites in blood||Level lower than expected||10%|
|ALL||Level of drug metabolites in blood||Level lower than expected||2%|
- Medication event monitoring system - a medication dispenser containing a microchip that records when the container is opened and from Partridge et al (2002)
In 1998, trials evaluating Tamoxifen as a preventative agent have shown dropout rates of around one-third:
- 36% in the Royal Marsden Tamoxifen Chemoprevention Study of 1998.
- 29% in the National Surgical Adjuvant Breast and Bowel Project of 1998.
In March 1999, the "Adherence in the International Breast Cancer Intervention Study" evaluating the effect of a daily dose of Tamoxifen for five years in ‘at risk’ women aged 35–70 years was
- 90% after one year
- 83% after two years
- 74% after four years
Coronary heart diseaseEdit
In one study, patients who did not adhere to beta-blocker therapy were found to be 4.5 times more likely to have complications of coronary heart disease than those who do comply.
Patients with diabetes are at high risk of developing coronary heart disease and usually have related conditions that make their treatment regimens even more complex, such as hypertension, obesity and depression which are also characterised by poor rates of adherence.
- Diabetes non-compliance is 98% in US and the principal cause of complications related to diabetes including nerve damage and kidney failure.
- Among patients with Type 2 Diabetes, adherence was found in less than one-third of those prescribed sulphonylureas and/or metformin. Patients taking both drugs achieve only 13% adherence.
- Hypertension non-compliance (93% in US, 70% in UK) is the main cause of uncontrolled hypertension-associated heart attack and stroke.
- In 1975, only about 50% took at least 80% of their prescribed anti-hypertensive medications.
There is a clear correlation between adherence with medication regimens and factors such as: relapse rates; hospitalisation rates; re-hospitalisation rates; incidence of serious unwanted events, including suicides; assaults or severe violence.
In 1997, non-adherent schizophrenic patients were over three times more likely to relapse than patients who take their medication. A systematic review investigated the effects of compliance therapy for schizophrenia:
In a 2006 study there was no clear evidence to suggest that compliance therapy was beneficial for people with schizophrenia and related syndromes but more randomised studies are justified for this intervention to be fully evaluated.
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