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Compliance (medicine)

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 the patient and the
health-care provider aect compliance, and a positive
physician-patient relationship is the most important factor in improving compliance,[1] although the high cost of
prescription medication also plays a major role.[2]

thought to reect better the diverse reasons for patients

not following treatment directions in part or in full.[6][8]
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.[9] It is noted that compliance may
only refer to passively following orders.[10] However, the
preferred terminology remains a matter of debate.[11][12]
In some cases, concordance is used to refer specically to
patient adherence to a treatment regimen that is designed
collaboratively by the patient with the physician, to dierentiate it from adherence to a physician-only prescribed
treatment regimen.[13][14] Despite the ongoing debate, adherence is the preferred term for the World Health Organization,[1] The American Pharmacists Association,[5]
and the U.S. National Institutes of Health Adherence Research Network.[15]

Compliance is commonly confused with concordance,

which is the process by which a patient and clinician make
decisions together about treatment.[3]
Worldwide, non-compliance is a major obstacle to the effective delivery of health care. Estimates from the World
Health Organization (2003) indicate that only about 50%
of patients with chronic diseases living in developed
countries follow treatment recommendations.[1] In particular, low rates of adherence to therapies for asthma,
diabetes, and hypertension are thought to contribute substantially to the human and economic burden of those
conditions.[1] Compliance rates may be overestimated in
the medical literature, as compliance is often high in the
setting of a formal clinical trial but drops o in a realworld setting.[4]

Concordance also refers to a current UK NHS initiative

to involve the patient in the treatment process to improve
compliance.[16] In this context, the patient is informed
about their condition and treatment options. They are
involved with the treatment team in the decision as to
which course of action to take, and partially responsible
for monitoring and reporting back to the team. Compliance with treatment can be improved by:

Major barriers to compliance are thought to include the

complexity of modern medication regimens, poor health
literacy and lack of comprehension of treatment benets, the occurrence of undiscussed side eects, the cost of
prescription medicine, and poor communication or lack
of trust between the patient and his or her health-care
provider.[5][6][7] Eorts to improve compliance have been
aimed at simplifying medication packaging, providing effective medication reminders, improving patient education, and limiting the number of medications prescribed

Selecting treatments in a way that minimizes sideeects, and discussing management of side eects
Prescribing the minimum number of dierent medications
Simplifying dosage regimen by selecting a drug or
using a sustained release preparation that requires as
few doses per day as possible[17]
Having open discussions around medication options,
and alternatives if the rst option is not tolerated

2 Societal impact


A WHO study estimates that only 50% of patients suffering from chronic diseases in developed countries follow treatment recommendations.[1] The gures are even
lower in respect to adherence rates for preventative therapies, and can be as low as 28% in developed countries.
citation needed
This may aect patient health, and aect the
wider society when it causes complications from chronic
diseases, formation of resistant infections, or untreated
psychiatric illness.

An estimated half of those for whom treatment regimens

are prescribed do not follow them as directed.[1] Until
recently, this was termed non-compliance, which was
sometimes regarded as meaning that not following the directions for treatment was due to irrational behavior or
willful ignoring of instructions. Today, health care professionals more commonly use the term adherence to
a regimen rather than compliance, because this term is


Compliance rates during closely monitored studies are 3 Compliance issues

usually far higher than in later real-world situations. For
example, one study reported a 97% compliance rate at the
beginning of treatment with statins, but only about 50% 3.1 Health literacy
of patients were still compliant after six months.[4]
Cost and poor understanding of the directions for the
The experience of Patient Connect Service Limited treatment (referred to as 'health literacy') are major barin the UK is that medicines prescribed for pre- riers to completing treatments.[23][24][25] There is robust
ventative purposes are especially likely not to be evidence for a correlation between education and physitaken as prescribed;[18] perhaps because people do cal health. Poor educational attainment is a key factor in
not feel immediately threatened or, in the case of the cycle of health inequalities.[26][27][28]
symptomless conditions such as raised cholesterol levels (hypercholesterolaemia) and raised blood pressure Educational qualications help to determine an individ(systemic hypertension), feel no obvious benets at uals position in the labour market, their level of income
the time of taking the medicines As patients are and therefore their access to resources.
asymptomatic, they may not see a need to take medication.
Some gures are available from the UK on non- 3.2


One in ve adults has a long-standing illness or disabil up to 90% of diabetes patients do not take their med- ity. In 2003, a national study for the UK Department
ication well enough to benet from that medication. of Health, more than one-third of people with poor or
very poor health had literary skills of Entry Level 3 or
33-50% of some cancer patients take less of their
anti-cancer medicine than required.
Low levels of literacy and numeracy were found in 2003
only 75% of patients with coronary heart disease to be associated with socio-economic deprivation. Adults
(CHD) take sucient medicine for it to be eec- in more deprived areas, such as the North East of Engtive.
land, performed at a lower level than those in less de Up to 75% of hypertensive patients do not adhere to prived areas such as the South East. Local authority tenants and those in poor health were particularly likely to
their medicine.
lack basic skills.[30]
41-59% of mentally ill patients take their medica- A 2000 analysis of over 100 UK local education authority
tion infrequently or not at all.[19]
areas found educational attainment at 1516 years of age
coronary heart disease and
33% of patients with schizophrenia dont take their to be strongly associated with
medicine at all, and 33% are poorly adherent.
One fth of UK adults in 1999 (nearly seven million peo Less than 27% of depressed patients adhere to their
ple) had problems with basic skills, especially functional
literacy and functional numeracy, making it impossible
for them to eectively take medication, read labels, folIn the UK, it has been estimated that if CHD patients low drug regimes, and nd out more. This was described
adhered to their medication, each year 40,000 to 50,000 as:
fewer people would have a stroke and 25,000 would not
have a heart attack.
The nancial cost to the UK National Health Service
(NHS), and thus to society, is also high:
CHD 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

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
Moser Report (1999)

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 93% with a high school graduate reading







adherence.[42] Comprehension, polypharmacy, living arrangement, multiple doctors, and use of compliance aids
In the U.S, the National Report Card on Adherence rates was correlated with adherence. A conservative estimate
Americans with chronic medical conditions with a grade says 10% of all hospital admissions are through patients
C+ on adherence to their medication[32] and this con- not managing their medication .
tributes to an estimated cost of $290 Billion annually[33] .
Adherence factors in children with various conditions
Increase in patient medication cost share was found to be
have been studied. Asthma is a disease where selfassociated with low adherence to medication [34] . The
management compliance is critical. Co-morbidites have
United States is among the countries with the highest
been noted that aect outcomes; electronic monitoring
prices of prescription drugs which is one of factors leadmay help.[43] Social factors of treatment adherence have
ing to the high healthcare costs. This is mainly attributed
been studied in the context of children and adolescent
to the governments lack of ability to negotiate lower
psychiatric disorders:
prices with monopolies in the pharmaceutical industry
especially with the brand name drugs [35] . In order to
Young people who felt supported by their family and
manage the medication costs, many patients on long term
doctor, and had good motivation, were more likely
therapies fail to ll their prescription or skip or reduce
to comply.[44]
doses. According to the Kaiser Family Foundation survey in 2015, approximately three quarters (73%) of the
Young adults may stop taking their medication in orpublic think the drug prices are unreasonable and blame
der to t in with their friends, or because they lack
pharmaceutical companies for setting prices so high [36] .
insight of their illness.[44]
In the same report, half of the public reported that they
Those who did not feel their condition to be a threat
are taking prescription drugs and quarter (25%) of those
to their social well-being were eight times more
currently taking prescription medicine report they or a
likely to comply than those who perceived it as such
family member have not lled a prescription in the past
a threat.[45][46]
12 months due to cost, and 18 percent report cutting pills
in half or skipping doses [37] . In comparison to Canada,
Non-adherence is often encountered among children
only 8% of adults reported to have skipped their doses
and young adults; young males are relatively poor at
or not lling their prescriptions due to the cost of their
prescribed medications .

3.5 Ethnicity

People of dierent ethnic backgrounds have unique adBoth young and elderly status are associated with non- herence issues through literacy, physiology, culture or
poverty. There are few published studies on adherence
The elderly often have multiple health conditions, and in medicine taking in ethnic minority communities. Etharound half of all NHS medicines are prescribed for peo- nicity and culture inuence some health-determining beple over retirement age, despite representing only about haviour, such as participation in screening programmes
20% of the UK population.[39][40] The recent National and attendance at follow-up appointments.
Service Framework on the care of older people high- Prieto et al [51] also emphasised the inuence that ethnic
lighted the importance of taking and eectively managing and cultural factors can have on adherence. They pointed
medicines in this population. However, elderly individu- out that groups dier in their attitudes, values and beliefs
als may face challenges, including multiple medications about health and illness. This view could aect adherwith frequent dosing, and potentially decreased dexterity ence, particularly with preventive treatments and medior cognitive functioning. Patient knowledge is a concern cation for asymptomatic conditions. Additionally, some
that has been observed.
cultures fatalistically attribute their good or poor health to
Cline et al. identied several gaps in knowledge
about medication in elderly patients discharged from
hospital.[41] 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-

their god(s), and attach less importance to self-care than

Measures of adherence may need to be modied 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.

3.6 Prescription ll rates

While a health care provider visit with a patient may result
in the patient leaving with a prescription for medication,

not all patients will ll the prescription at a pharmacy. In
the U.S., 20-30% of prescriptions are never lled at the
pharmacy.[52][53] There are many reasons patients do not
ll prescriptions including the cost of the medication,[2][5]
doubting the need for medication, or preference for selfcare measures other than medication.[54][55] Cost may be
a barrier to prescription drug adherence, but convenience,
side eects and lack of demonstrated benet are also signicant factors to a complex situation. A US nationwide
survey of 1,010 adults in 2001 found that 22% chose not
to ll prescriptions because of the price, which is similar to the 20-30% overall rate of unlled prescriptions.[2]
However, analysis by health insurers suggest that patient
co-payment requirements can be reduced to $0 with little
or no improvement in long-term adherence rates.
Prescription medical claims records are commonly used
to estimate medication adherence based on ll rate. Patients are routinely dened as being 'Adherent Patients
if the amount of medication furnished to the patient is
at least 80% based on days supply of medication divided
by the number of days patient should be consuming the
medication. This quantity is dened as the medication
possession ratio (MPR). However, recent work by several
investigators has suggested that MPR of 90% or above
may be a better threshold for deeming consumption as


3.7 Course completion

Once started, patients seldom follow treatment regimens as directed, and seldom complete the course of
treatment.[5][6] In respect of hypertension, 50% of patients completely drop out of care within a year of
diagnosis.[58] Persistence with rst-line single antihypertensive drugs is extremely low during the rst year of
treatment.[59] As far as lipid-lowering treatment is concerned, only one third of patients are compliant with at
least 90% of their treatment.[60]
As mentioned previously, the World Health Organization
(WHO) has estimates that only 50% of people complete
long-term therapy for chronic illnesses as they were prescribed, which puts patient health at risk.[61] For example, statin compliance drops 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.[62]

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 dierent labels for increasing patient understanding
of directions.[63][64] For example, medications are sometimes packed with reminder systems for the day and/or
time of the week to take the medicine.[63] With the objective to support patient adherence to medicinal therapy, a
not-for-prot organization called the Healthcare Compliance Packaging Council of Europe (HCPC-Europe) was
set up between the pharmaceutical industry, the packag3.6.1 Medication Possession Ratio
ing industry and representatives of European patients organizations. The mission of HCPC-Europe is to assist
and to educate the healthcare sector in the improvement
There are two forms of MPR that can be calculated,
of patient compliance through the use of packaging soluxed and variable.[57] The calculation of either is relations. A variety of packaging solutions have been develtively straightforward, for Variable MPR (VMPR) it is
oped by this collaboration to aid in patient compliance.
calculated as the number of days supply divided by the
The failure to complete treatment regimens as prescribed
number of elapsed days including the last prescription.
has signicant negative health impacts worldwide.[1] Exsupply days All
amples of the rate and consequences of non-compliance
prescription) last of (inclusive days Elapsed
for selected medical disorders is as follows:
For the Fixed MPD (FMPT) 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
3.8 Asthma
within the year that the patient has been prescribed.
supply days All 365
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.

Asthma non-compliance (28-70% worldwide) increase

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: dicult inhaler use, side eects
of medications, and cost of the treatment.[65]
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


Coronary heart disease

stop taking a steroid inhaler is with a doctors approval.[66]

3.10 Coronary heart disease

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
200,000 new cases of cancer are diagnosed each year in do comply.
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% 3.11 Diabetes
of all deaths in the UK. However:
Diabetes non-compliance (98% in US) is the principal cause of complications related to diabetes in 90% of cancer pain can be eectively treated, yet
cluding nerve damage and kidney failure.
only 40% of patients adhere to their medicines due
to poor understanding.
Among patients with Type 2 Diabetes, adherence
is found in less than one-third of those prescribed
sulphonylureas and/or metformin. Patients taking
The reasons for non-adherence have been given by paboth drugs achieve only 13% adherence.[71]
tients as follows:



The poor quality of information available to them 3.12 Hypertension

about their treatment.
Hypertension non-compliance (93% in US, 70% in
A lack of knowledge as to how to raise concerns
UK) is the main cause of uncontrolled hypertensionwhilst on medication.
associated heart attack and stroke.
Concerns about unwanted eects.
In respect of anti-hypertensive therapy, only
about 50% take at least 80% of their prescribed

Issues about remembering to take medication.

Partridge et al (2002) [67] identied evidence to show
that adherence rates in cancer treatment are variable, and
sometimes surprisingly poor. The following table is a
summary of their ndings:

4 Health and disease management

4.1 Asthma

Medication event monitoring system - a medication

dispenser containing a microchip that records when
the container is opened and from Partridge et al

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 dierences between the
types of inhalers and telling patients that steroid inhalers
Other trials evaluating Tamoxifen as a preventative agent
will need to be taken every day can help to improve adhave shown dropout rates of around one-third:
herence in this population.[73]
36% in the Royal Marsden Tamoxifen Chemopre4.2
vention Study.[68]


29% in the National Surgical Adjuvant Breast and Patients with diabetes are at high risk of developing
Bowel Project.[69]
coronary heart disease and usually have related conditions that make their treatment regimens even more comAccording to correspondence in the Lancet in March plex. These related conditions, such as hypertension,
1999,[70] the Adherence in the International Breast Can- obesity and depression are also characterised by poor
cer Intervention Study (evaluating the eect of a daily rates of adherence, and therefore exacerbate treatment
dose of Tamoxifen for ve years in at risk women aged outcomes.[74][75]
3570 years) was:
90% after one year
83% after two years
74% after four years

4.3 Hypertension
As a result of poor compliance, 75% of patients with a
diagnosis of hypertension do not achieve optimum bloodpressure control.




5.2 Technology

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.

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. Already there are multiple opportunities to use technology to boost patient compliance rates, and make it easier
Non-adherent schizophrenic patients are over three times
for patients to become involved in their own care. As
more likely to relapse than patients who take their medipart of the push to encourage implementation of elec[76]
tronic health records in hospitals and private practices,
the US government has set meaningful use objectives
and benchmarks. One such objective is the use of a pa4.5 Stroke
tient portal, through which patients can securely view lab
Survivors of stroke or heart attack frequently have dis- reports, request prescription rells, and ask questions of
their providers - all of which can increase patient compliability and worse health:
ance with care plans.
15-50% of stroke patients suer with major depres- Another medium to boost compliance is mobile technology. Both physicians and patients are using tablets,
smartphones, and other devices in increasing numbers,
20% will go on to develop dementia as a result of all of which can be equipped with any number of medithe stroke.
cal apps to help with patient monitoring and compliance.
Text-message reminders are increasingly being used to
Faecal incontinence is common after a severe stroke,
help with patient compliance; studies show that daily text
bringing stress to both the individual and the family.
messages sent to remind patients to take their medication
5% will have untreatable severe pain, that dominates have improved compliance rates and patient health - especially in younger patients with chronic illnesses such as
their life.
diabetes, and young women who take contraceptives. [79]

Improving compliance rates

Patients adherence with their medication is poor across

all chronic diseases, including coronary heart disease,
mental health, diabetes and cancer. This poor adherence
results in signicant increase in illness, disability, symptoms and even death.
Care in choice of medicine by the prescribing physician,
along with and the provision of greater information to the
patient can improve compliance. For example, patients
taking typical antipsychotics tend to experience more severe side-eects, and also receive less information about
their illness, medicines and side-eects.[77] They were
naturally more likely to be non-compliant than those receiving atypicals.

As telemedicine technology improves, physicians will

have better capabilities to remotely monitor patients
in real-time and to communicate recommendations and
medication adjustments as the situation demands, rather
than waiting until the next oce visit. Telemedicine using personal mobile devices, such as smartphones, will
become increasingly important for monitoring patients
with chronic conditions such as cardiovascular disease
and diabetes.[81]

Medication Event Monitoring Systems, in the form of

smart medicine bottle tops (MEMS or eCAP), smart
pharmacy vials (eCAP or NantHealth's GlowCap) or
smart blister packages (Med-ic or Cerepak) are frequently used in clinical trial and other applications where
exact compliance data are required. Such systems usually 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
5.1 The role of health care providers
read via proprietary readers, or NFC enabled devices,
Health care providers play a great role in improving such as smartphones or tablets. There is evidence that
adherence issues. Providers can improve patient in- the use of such devices can help improve e.g. control of
teractions through motivational interviewing and active hypertension.[82]
There have been a number of initiatives involving real
Health care providers should work with patients to devise a plan that is meaningful for the patients needs. A
relationship that oers trust, cooperation, and mutual responsibility can greatly improve the connection between
provider and patient for a positive impact.[10]

time adherence monitoring. What real time means is

debatable. 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 bro-


Patient information

ken 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 dicult 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. Again, it doesn't 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, 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 (Such
as Med-ic Electronic Compliance Monitor by Information Mediary Corp.). 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 eort required
to equip every single blister with a SIM module and expensive monthly data subscription.

for smart adherence management is in clinical trials. This
is also where most of the existing devices are being used
at the moment.

5.3 Patient information

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 together completed a 200,000 patient study into the
eect of pharmacists providing to patients the information that patients want. The results of the survey show that
where a pharmacist talks through the leaet given to the
patient, then there is an increase in adherence by between
16% and 33% within three months.[83]

The question of real time is not solved by simply generating data which is based on a proxy of ingestion. If such Since then, millions of patients have been supported, and
data isn't being parsed and used in an eective fashion to had measurable impact across the following therapy arassist patients, caregivers and medical professionals with eas:
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 ction 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 eective solution and
unrealistic expectations derived from over condent presentations, the entire eld of smart adherence monitoring
is in danger of being ignored.
For the time being, the most applicable eld of endeavour alt-Alt


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See also
Polypharmacy and pill burden


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External links
Adherence to long-term therapies, a report from the
World Health Organization
Ten hurdles to patient adherence

Application for monitoring therapy compliance

Technology report on NFC enabled smart medication packages



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