pharm care medicines adherence · 5 search terms the term compliance is used if the research is...
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Evidence Search and Synthesis NHS Education for Scotland
Title Pharmaceutical care and interventions to promote medicines adherence
This document summarises current evidence on pharmaceutical care and
interventions to promote medicines adherence, and indicates where systematic
reviews are lacking.
Contents
Evidence Search and Synthesis NHS Education for Scotland ..................................................... 1
Title Pharmaceutical care to promote medicines adherence ................................................ 1
1 Key Messages ........................................................................................................................... 2
2. Systematic review gaps ......................................................................................................... 2
3 Background ................................................................................................................................ 2
4 Question(s) ................................................................................................................................. 3
5 Scope of this summary ............................................................................................................. 4
6. Results ....................................................................................................................................... 5
7. Narrative summary .................................................................................................................. 6
8. References ............................................................................................................................. 15
Appendix 1 – Search Strategy.................................................................................................. 19
Appendix 2 .................................................................................................................................... 21
Note
This review was produced by staff at NHS Education for Scotland. Although the
evidence has been sourced and compiled systematically, it is not a systematic
review. This review summarises relevant evidence from pre-appraised studies in
systematic reviews; it does not make recommendations.
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1 Key Messages
key messages from all questions and sub-questions
• Pharmaceutical care is defined as the provision of medicines, with the
involvement of the patient and other healthcare professionals, to support a
positive treatment outcome and improve the patient's quality of life. [24]
• Interventions include pharmacist-led services, patient reminder systems [15,
20,22], incentives [11], simplified dosing regimens [9], method of medicines
administration, new technology e.g. text messaging [15], internet-based
services [16]
• Adherence measures include Medication Event Monitoring System (MEMS)
pill bottle caps, pill counts, routine pharmacy refills
• Variety of interventions, no particular intervention could be identified, which
improved both adherence and clinical outcomes
2. Systematic review gaps
A summary of research gaps
• More guidelines and protocols required for researchers to design studies
monitoring adherence
• More objective adherence measures required
• Adherence and sustainability of interventions required to be measured in the
long term
• More research required to establish reasons for non-adherence
• More research required to study patients whose adherence is low
• More research required to study the clinical outcomes
• New technology- requirements to study user preferences, effectiveness and
confidentiality issues (e.g. for text messages sent to smart phones)
3 Background
Why is this question important?
This research topic supports the Scottish Government's 2020 vision [1], which aims
to assist patients in managing their conditions at home with appropriate support from
healthcare professionals. The Review of NHS Pharmaceutical Care of Patients in the
Community in Scotland [24] considers the role of pharmaceutical care in delivering
the Scottish Government's 20:20 vision of healthcare to achieve person-centred,
safe and effective patient care and forms the basis of Prescription for Excellence [3].
As part of the vision outlined in Prescription for Excellence [3], pharmacists have an
important role in helping the patient to manage their own condition and also to
promote the safe and effective use of medicines. Currently many drugs are not taken
as prescribed for a variety of reasons. Pharmaceutical care aims to improve
medicines adherence by utilising interventions to assist the patient in taking
medication as prescribed.
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A survey was recently sent out by NHS Education for Scotland to pharmacists to
discover their preferences for and the main areas of information required from a
literature search, the outcomes of which would support their work. From the
competed survey questionnaires, it was established that pharmaceutical care and
medicines adherence was one of the top 3 topics.
4 Question(s)
Topic: Is there evidence that pharmaceutical care promotes medication adherence?
Subquestions:
1. What is a pharmaceutical care programme?
2. What compliance aids are available?
3. What is the evidence for and against the use compliance aids in pharmaceutical
care to support medicines adherence?
4. What is the role of compliance devices?
The review considers medidose (also called dosette) boxes, as well as other
alternative interventions/compliance aids. Resources for all healthcare professionals
are included, as dosette boxes may be given to patients by pharmacists, doctors,
social care staff, home care assistants and support workers.
The setting for the review is in the community, where patients of all ages have to
take their medicines themselves. All populations are included in the review. It was
expected that there would be many results for elderly people as they take many
different drugs but also results for young people on drugs for chronic conditions,
such as asthma.
Initially, it was decided that the review would consider medicines for all health
conditions. All conditions were considered at the search stage, however the following
conditions were later excluded as the reasons for non-adherence would differ:
mental health conditions, optometry, dermatology and conditions where medication
was for prevention e.g. stroke, diabetes, transplants, cardiovascular conditions.
Drugs have trade names (used in the community setting) and generic names (used
in hospital setting) and it was expected that literature may mention patient confusion
about the different names of medicines.
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5 Scope of this summary
Methods
This evidence summary was part of a pilot project looking to establish a new service
within NHSScotland. The model for evidence summaries was designed by NES and
EPPI Centre.
A systematic search of four relevant health and social care databases was
conducted during January/February 2015: The Cochrane Library, Health Systems
Evidence, and Epistemonikos. As well as these databases Scottish Intercollegiate
Guidelines Network (SIGN), National Institute for Health and Care Excellence
(NICE), National Guidelines Clearing House, Clinical Knowledge Summaries, the
Royal Pharmaceutical Society, General Pharmaceutical Council and Community
Pharmacy Scotland websites were searched. The search was conducted for studies
published in English and citations were imported to EPPI Reviewer 4 software for the
selection and screening process. Citations were assessed for relevance and had to
meet all of the following inclusion criteria:
• systematic reviews or guidelines providing context/background information on
the topic
• English language,
• 2 main Cochrane reviews & reviews published after 2012 - Feb 2015,
• countries: UK, US, OECD countries where possible (sometimes countries not
stated in review)
• relevant setting: community and not hospital settings
• age group: all ages
Reasons for exclusion:
• Reasons for non-adherence or barriers to adherence
• Reviews assessing whether adherence improved outcomes
• Reviews where improving adherence seemed to be only a small part, not the
primary goal of the review.
• Mental health topics as adherence issues can be for a range of reasons
• Disease specific references concerning prevention as again this has many
causes therefore stroke, diabetes , transplant, CHD
• Dermatology as creams again have many reasons of lack of compliance and
cannot be generalised
• Optometry/teaching patients how to use eye drops
• No access to full text
• Duplicate resource
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Search Terms
The term compliance is used If the research is more than 7 years old, as the patient
was given directions to take the medicine. More recent publications will use the
terms adherence or concordance, as a discussion with patient would take place to
encourage them to take the medicine.
Medicines optimisation was also a term retrieved in the search results [National
Institute for Health and Care Excellence, Royal Pharmaceutical Society] This term
appears to have a broader focus than just adherence. In England, the concept of
medicines optimisation is underpinned by four key principles: i)understanding the
patient experience; ii) evidence-based choice of medicines; iii) ensuring that
medicines use is as safe as possible; and iv) making medicines optimisation part of
routine practice. [Royal Pharmaceutical Society]
PICO Formula
P
(population,
patient,
condition)
All patients, all ages, community setting, all conditions (some
conditions later excluded after review of search results)
I (Intervention;
drug,
diagnostic test,
exposure)
Compliance aids, compliance devices, medidose, dosette boxes,
all drugs, interventions, pharmaceutical care
C (comparison) A group who did not get the dosette/medidose boxes, no
interventions
O (outcome) Better management of illness e.g. less gp appointments, patients
reporting better management of symptoms – better adherence to
medicines
For details of search strategy see Appendix 1
6. Results
In total 73 resources were initially identified. After applying exclusion criteria, the
number of included resources was reduced to 22, including 18 reviews and 4
guidelines.
There were 2 core Cochrane reviews, which provided the basis of the evidence.
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The 2014 Cochrane review by Nieuwlaat [17] et al. Evaluated interventions for
enhancing medication adherence, which updated a previous Cochrane review from
Ryan et al.[19] Searches for further reviews published since the main 2 reviews
produced 16 more reviews.
Context
Some of the studies were conducted outside Scotland. In countries where there is a
charge for prescriptions, the ability to pay for treatment would be an additional factor
to consider when assessing patients’ adherence to medicines.
What the authors of this evidence summary found
7. Narrative summary
Evidence
This section indicates how the included reviews answer some of the sub-questions
of this evidence summary.
1. What is a pharmaceutical care programme?
Pharmaceutical care is described in Wilson et al. [24] as the provision of
medicines, with the involvement of patient and other healthcare professionals,
to support a positive treatment outcome and improve the patient's quality of
life. Aspects of pharmaceutical care outlined in the review by Nieuwlaat et al.
[17] include education, motivational interviewing, daily treatment support and
sometimes also the extension of support to patient’s families. Ryan et al. [19]
recognised that interventions, which directly involved pharmacists in
medicines management (eg medicines reviews) seemed to improve
medicines adherence.
No reviews were found with a primary focus on pharmaceutical care
programmes, however the guidelines provided some examples. There were 3
guidelines about the improvement of patient involvement in the decision-
making process. A local NHS Greater Glasgow and Clyde guideline [5] and a
NICE guideline from 2009 [4], help healthcare professionals to find effective
ways of communicating information to patients with literacy, language
problems or physical disabilities.
The NHS Greater Glasgow and Clyde guideline [5] illustrates medication aids
and medication reminder charts to overcome problems with dexterity,
memory, visual or hearing impairment, literacy or language problems or
learning disabilities. In addition, the NICE guideline [4] recommends the
appropriate action required when a patient makes an informed decision not to
take the medicine and provides advice for approaching non-adherence in a
non-judgemental way.
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Section 8 of the guideline (Interventions to increase adherence to prescribed
medicine) is particularly relevant, as it includes information about changing
dosing regimens, packaging, multi-compartment medicine systems,
formulation, reminders, patient information, therapy, disease self-monitoring.
The more recent NICE guideline from 2015 on Medicines optimisation [3]
updates and replaces recommendation 1.4.2 in the 2009 NICE guideline on
medicines adherence, which concerned patient transfer between services (for
example, between hospitals and care homes or on discharge from hospital)
The MCA Toolkit by Oboh et al. [6] reviews use of MCAs for older people and
provides case study examples and practical exercises for pharmacists in NHS
East & South East England Specialist Pharmacy Services.
2. What compliance aids are available?
The review by Ryan et al. [19] lists a range of interventions to promote
medicines adherence, including additional services provided by pharmacists
to patients. Reminders can come in the form of pillboxes, blister packaging,
calendar packs, appointment cards, medicines charts, alarms and memory
aids. Incentives can be given to the patients and dosing regimens can be
simplified. Methods of administration could be changed from injected to oral
medicines in some cases. Letters, postcards, could be sent to patients or
there could be follow-up by telephone.
Various compliance aids were mentioned in the additional reviews including
multi-compartment compliance aids [17,18] packaging interventions [6,9],
multimedia educational interventions [7], dosing frequencies [9], incentives
[11], electronically compiled drug dosing histories/device dose memory
functions [11], cognitive based behaviour change techniques [12], new
technology (mobile phone text messaging [15] and smartphone/tablet self
management apps [16] patient reminders
3. What is the evidence for and against the use compliance aids in
pharmaceutical care to support medicines adherence?
Intervention type: reviews of all interventions
The latest Cochrane review of all interventions is Nieuwlaat et al [17], this
review differed from the earlier review by deliberately not classifying by
intervention type, as often the interventions include a combination of complex
interventions rather than just one. The review outlines the complexity of
interventions currently used to improve medicines adherence and often the
effectiveness is not proven. Studies in the review with the lowest risk of bias
tended to be the complex interventions. To improve adherence, frequent
communication with the patient is required for the duration of the treatment.
[17]
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The previous review by Ryan et al. highlighted that there is not one
intervention that could be used in every situation to improve adherence for
every condition, medicine or person. Findings showed that medicines reviews,
changing dosing regimens and self monitoring/management improved
adherence. The effects of reminders and packaging in combination with other
interventions were inconsistent. More evidence is required for certain
populations, including children, carers and patients with multiple
conditions.The range of interventions included in Ryan’s review is listed in
above in question 2 and the quality of the included studies was high, as low
quality non-Cochrane studies were excluded.
Intervention type: multi-compartment compliance aids
The term MCA covers a variety of devices for re-packaging medicines in
Individual compartments.
The Royal Pharmaceutical Society (RPS) review was based on evidence from
quality sources such as NICE guidelines and a Cochrane review. The RPS
defines a multi-compartment compliance aid as a repackaging system for
solid dosage form medicines, such as tablets and capsules, where the
medicines are removed from manufacturer’s original packaging and
repackaged into the MCA. Repackaging systems can include monitored
dosage systems (MDS) and daily dose reminders. There are new MCA
systems, which are able to accommodate liquid dosage forms. MCA’s exist as
either sealed or unsealed systems, and cassette (where several medicines
can be in one compartment) or blister (where there is only one dose of a
medication in each compartment) systems.
Pharmaceutical companies must ensure packaging used for medicines
provides protection against water vapour, atmospheric gases and light.
Unsealed MCA’s have a series of compartments with sliding lids and provide
no significant barrier to water vapour & atmospheric gases, any light is
blocked out by the cover. Sealed MCA’s include blister type packaging and
the barrier to water vapour and atmospheric gases is reported to be better
than for unsealed MCA [18]
MCA’s can be bought by patients or provided by pharmacists.
The guidelines produced by Oboh et al. [6] stated that multi-compartment
compliance aids can be a reminder/prompt for the patient to take their
medicines and is a means of simplifying a complex drug regimen. Carers and
relatives may find it a useful way to support the patient.
However the review also provides evidence against the use of MCAs as they
can only be used for solid oral tablets.
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Some medicines cannot be put in MCA's as it interferes with effectiveness.
Drugs may need to be kept in special conditions (eg. temperature, light,
moisture) Medicines need to be taken according to instructions, which may
not be available in box. Patients can become confused about what they have
taken.
Both Obah [17] and the Royal Pharmaceutical Society’s (RPS)[18] reviews
cite the possibility of safety concerns caused by medicines interacting when
several drugs are contained within a single MCA compartment. The RPS [18]
review found insufficient data on the stability of medicines when stored
outside of the manufacturer’s original packaging.
RPS refers to 2012 report which states MCA's may save staff time,
standardise processes in nursing homes or reduce incidence of medication
errors but the authors also reported insufficient evidence to support the
benefits of MCA in improving medicines adherence in patients. If other
systems of medicines administration are required in addition to MCA (for
example where the formulation or dosage of medicines are not suitable for
inclusion within an MCA) this introduces complexity and potential confusion.
Intervention type: packaging interventions
The review by Boeni [6] et al. was based on 30 studies, of which the
methodological quality was strong for 5 studies. This review highlights the
requirement for further studies, which focus on the effects on patient safety.
The studies included in their review did suggest that drug reminder packaging
had a positive effect on adherence and clinical outcomes but as the quality of
these studies was regarded as low, the authors were unable to provide firm
conclusions about effects of packaging. Average age of participants 62 year
old (participants 38-87 years). They took average 3.9 medications (range 1-9)
during a period of 5.4 months (range 7days to 14mth) for a wide range of
conditions.
However in the review by Conn [9] et al. the meta-analysis findings did
support the use of pill boxes and blister packs to effectively increase
medication adherence for ageing adults with multiple chronic conditions,
although the authors noted that the results could vary depending on the
number of medicines prescribed and that there were indications of publication
bias.
One advantage of the use of pill boxes/blister packs for patients with memory
problems was that the patient could see if he/she had taken a dose or not.
The patient would also know which medicine to take at which time and would
not need to open multiple containers. The patient’s carers could see if the
patient is taking the medicine out of the pill box/blister pack.
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There are also benefits for healthcare professionals as pillboxes can be given
for a longer duration, compared to interventions such as counselling. A pill
box required less effort than a blister pack, which is prepared by a pharmacist
and it is a relatively cheap intervention.
The disadvantages of this method were that packaging interventions were
good for non-intentional non-adherence but not deliberate non-adherence.
The packaging might not be child-resistant and pill boxes/blister packs cannot
record the time the patient took the previous dose.[9]
Intervention type: multimedia educational interventions
Multimedia education programs provide information using a combination of
audio with graphic presentation of information and may use animations or
video. Multimedia study interventions were videos 3-30 minutes long,
computer programmes or computer games, which participants viewed at least
once.
Multimedia resources may be useful for overcoming barriers such as low
literacy levels, as learning improved when presentations included audio as
well as visual format. Multimedia programmes use portable technologies or
can be accessed over the internet at any time and the recipient can alter the
pace for viewing and included information can be adapted to suit needs of
individual patients. To examine adverse effects one of the included studies
monitored possible stress or anxiety using the educational programme.
The review by Ciciriello et al. [7] suggested that multimedia was as effective
as written education or brief education from a health provider but it did not
improve adherence to medications compared with usual care or no education.
(Although there is a note of caution as the findings were based on a small
number of low quality studies) Written education included patient information
leaflets, printed instruction sheets. Usual care included education or
presentations provided verbally by doctors, pharmacists or nurses as personal
or group instruction. This review considered multimedia education programs
for patients of all ages, including children and carers.
Overall, there was not enough evidence to recommend it as a replacement for
written education or education by a health professional. The authors
suggested that multimedia could be used instead of detailed education given
by a health provider when the health professional was not available.
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Intervention type: dosing frequencies
In the review Coleman et al. [9] adherence levels, for the duration of at least
one month, were found to improve in patients taking oral medications for
chronic diseases when they were prescribed once-daily rather than more
frequently scheduled medication regimens, based on electronic measurement
of adherence. However the authors noted that even the use of once-daily
regimens did not guarantee perfect adherence, as other factors were
involved. Three studies on asthma found the adherence rate to be less than
other diseases, such as cardiovascular disease. However there was not
enough available information to provide a specific reason for this non-
adherence. The included epilepsy and asthma studies enrolled younger
adults, while the average age of other study participants was between 50 and
70 years. The age factors match the expectations in the original search
question. In most studies, the proportions of men and women were
approximately equal, except for 1 study enrolling only women and 4 studies
that enrolled only men. Adherence rates increase when patients know they
are being watched. There are limitations to monitoring adherence as the use
of electronic devices is not a natural process. Self-reports are not always
accurate either as they rely on patients’ memory, honesty etc, and blood-level
monitoring can only test if the patient took the latest dose. Refills cannot
indicate when the patient took the dose. Adherence rates declined over
longer follow-up periods of over 6 months.
Intervention type: incentives
Studies included in the review by DeFulio et al. [11] assessed the
effectiveness of material incentives including money per dose taken or
vouchers, prizes, access to paid job training, small toys for children and
meals.
The authors found that incentive-based medication adherence interventions
could be very effective, but there were few controlled studies included in the
review. Patients involved in studies on incentive-based medication adherence
interventions were often taking medication for drug or alcohol dependence,
HIV, or latent tuberculosis. The intervention had a greater impact when the
patient valued the incentive more. The study durations varied from 4 weeks to
6 months. The authors highlighted a need for more high-quality evaluations of
the effectiveness of these interventions and also to determine the conditions
that make the intervention effective.
Intervention type: electronically compiled drug dosing histories/device dose
memory functions
Electronic medication-event monitoring involves the automatic creation of a
record of the time history of each patient’s entry into the drug package.
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Medication event monitoring systems (MEMS) have a microprocessor in the
medicine bottle top and it provides time-stamped records of the number of
times it was opened. Dose-memory and dose-reminder functions store and
display dose-history information and reminders can be set by the patient. One
example of a dose-memory function device is a diabetes insulin pen.
Evidence in the review by Demonceau et al. suggested that electronically
compiled drug dosing histories are useful for healthcare professionals to
provide feedback. However the author mentions methodological weaknesses
in the study designs and methods, as a result identifying interventions that
could effectively enhance adherence to medications became more
challenging. The review covered any intervention or combination of
interventions intended to affect adherence to self-administered prescribed
medications in short-term and in long-term therapy. Average age of
participants was 47, although five studies covered adherence-enhancing
interventions for children.
Hall et al. [13] reported similar findings as, healthcare professionals also
found it useful to access patient’s dose-histories to aid their management of
the disease. Other advantages were that devices could enhance patients'
motivation to manage their medicines and their condition and patients valued
the facility of the device to provide dose-history and reminders. Devices
helped to reduce forgotten or incorrect medication dosing. In their review,
asthmatics, diabetics and HIV patients reported improved treatment
adherence when provided with devices with dose memory or dose-memory
and dose-reminder functions. There were different study designs used
including observational studies and randomised control trials, studies
worldwide. Benefits of devices were found both for younger patients as well
as the elderly and patients with multiple chronic conditions.
Intervention type: cognitive based behaviour change and counselling
*Please note counselling is discussed in detail by the “Patient counselling for
prescribed medication” review.*
Easthall [12] describes cognitive based behaviour change (CBCTs) as
interventions which aim to change a patient's behaviour by altering their
thoughts, feelings, confidence or motivation to adhere. Motivational
interviewing encourages patients to consider any unintentional barriers to
adherence and problem solve to produce effective solutions. Behaviour
change counselling can be used for both intentional and unintentional non-
adherence. The authors found cognitive based behaviour change to be an
effective intervention and suggested that healthcare providers consider
including CBCTs in medication adherence consultations.
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A quality assessment of all included studies was made using the Cochrane
risk of bias tool.
Counselling was another psychological intervention highlighted by Van Camp
et al. [21] as being an effective way for nurses to use in addition to other
methods for improving adherence. The quality of studies in Van Camp’s
review was acceptable to high. Complex interventions tailored counselling in
combination with social support, education and reminders. The interventions
were mainly for patients with HIV. The duration of counselling in all but one of
the included articles was for 3 months or less.
Intervention type: new technology
The effectiveness of mobile phone text messaging was reviewed by Kannisto
et al. [15] Mobile phone text messages were the only intervention in some of
the included studies, in other studies it was in conjunction with another
intervention. Text message reminders were often sent daily. The time the
reminders were sent could vary depending on whether it was for a medicine to
be taken or for a patient to attend a scheduled appointment. More studies
using randomised controlled trials are required before a firm conclusion on
effectiveness can be made. However 77% (46/60) of the studies showed
improved outcomes. In addition to text messages, smartphone apps were also
mentioned as a way of aiding patients in their self-management of asthma
[Marcano,15]. Similar to the text messages, there were studies where the
apps were used as the only intervention, and others where they were used in
conjunction with another intervention. Where more than one intervention was
used, a requirement for further research analysis of the effect of each
intervention separately was stated. Problems with apps could include poor
usability or technical difficulties with mobile health app or hardware. It is
important to ensure that any recommendations made in the app are supported
by current evidence, as health apps that provide incorrect misleading info may
harm patients if they follow the guidance. There are also barriers to access,
one of the US studies found that use of the apps was mainly by wealthy, well-
educated, individuals younger than 45, who were urban or suburban
residents. [15]
4. What is the role of compliance devices?
The role of compliance devices is to remind the patient when to take the
correct medicine and there were many studies about reminder interventions.
Compliance devices can also be used to assist patients with any physical,
literacy or language barriers to take their medicines.[5] Carers may also find
the devices useful to support patients in taking their medicines.
14
Some devices also had a means of reporting dose histories, the role of these
devices would also be to inform the healthcare professional about medicines
uptake to enable them to take appropriate action, such as providing the
patient with further information or investigating reasons for non-adherence.
15
8. References
Links to Policy
1 2020 vision transfer from hospital care to primary care in the community
http://www.scotland.gov.uk/Topics/Health/Policy/2020-Vision
2 Prescription for Excellence: A Vision and action plan for the right
pharmaceutical care through integrated partnerships and innovation Scottish
Government (2013)
http://www.scotland.gov.uk/Topics/Health/Policy/Prescription-for-Excellence
Guidelines
3 National Institute for Health and Care Excellence; (2015) Medicines
optimisation: the safe and effective use of medicines to enable the best
possible outcomes. . : .
4 Nunes V, Neilson J, O’Flynn N, Calvert N, Kuntze S, Smithson H, Benson J,
Blair J, Bowser A, Clyne W, Crome P, Haddad P, Hemingway S, Horne R,
Johnson S, Kelly S, Packham B, Patel M, Steel J (2009) Clinical Guidelines
and Evidence Review for Medicines Adherence: involving patients in
decisions about prescribed medicines and supporting adherence..
http://www.nice.org.uk/guidance/cg76/evidence/cg76-medicines-adherence-
full-guideline2
5 NHS Greater Glasgow; Clyde (2012) Managing medication guidance: To
assist healthcare professional to assess patients experiencing medication
compliance problems. http://www.rpharms.com/support-pdfs/managing-
medication-guidance.pdf
6 Oboh Lelly (2013) Supporting older people in the community to optimise their
medicines including the use of multi compartment compliance aids (MCAs)
Vs3. http://www.medicinesresources.nhs.uk/en/Communities/NHS/SPS-E-
and-SE-England/Meds-use-and-safety/Service-deliv-and-devel/Older-people-
care-homes/MCA-Toolkit-Vs3-Jun13/
Systematic reviews which met the inclusion criteria
7 Boeni F, Spinatsch E, Suter K, Hersberger KE, Arnet I (2014) Effect of drug
reminder packaging on medication adherence: a systematic review revealing
research gaps.. Systematic reviews. 3(1): 29.
http://www.systematicreviewsjournal.com/content/3/1/29
16
8 Ciciriello Sabina, Johnston Renea V; Osborne Richard H; Wicks Ian, deKroo
Tanya, Clerehan Rosemary, O'Neill Clare, Buchbinder Rachelle (2013)
Multimedia educational interventions for consumers about prescribed and
over-the-counter medications. Cochrane Database of Systematic Reviews.
(4): .
9 Coleman CI, Limone B, Sobieraj DM, Lee S, Roberts MS, Kaur R, Alam T
(2012) Dosing frequency and medication adherence in chronic disease..
Journal of managed care pharmacy : JMCP. 18(7): 527-39.
http://www.amcp.org/WorkArea/DownloadAsset.aspx?id=15582
10 Conn VS, Ruppar TM, Chan KC, Dunbar-Jacob J, Pepper GA, De Geest S
(2014) Packaging interventions to increase medication adherence: systematic
review and meta-analysis.. Current medical research and opinion. 31(1): 1-47.
http://informahealthcare.com/doi/abs/10.1185/03007995.2014.978939
11 DeFulio A, Silverman K (2012) The use of incentives to reinforce medication
adherence.. Preventive medicine. 55 Suppl: S86-94.
http://www.sciencedirect.com/science/article/pii/S0091743512001600
12 Demonceau J, Ruppar T, Kristanto P, Hughes DA, Fargher E, Kardas P, De
Geest S, Dobbels F, Lewek P, Urquhart J, Vrijens B, ABC project team;
(2013) Identification and Assessment of Adherence-Enhancing Interventions
in Studies Assessing Medication Adherence Through Electronically Compiled
Drug Dosing Histories: A Systematic Literature Review and Meta-Analysis..
Drugs. 73(6): 545-62.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647098/
13 Easthall C, Song F, Bhattacharya D (2013) A meta-analysis of cognitive-
based behaviour change techniques as interventions to improve medication
adherence.. BMJ open. 3(8): .
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740257/
14 Hall RL, Willgoss T, Humphrey LJ, Kongsø JH (2014) The effect of medical
device dose-memory functions on patients' adherence to treatment,
confidence, and disease self-management.. Patient preference and
adherence. 8: 775-788.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4043803/
15 Kannisto KA, Koivunen MH, Välimäki MA (2014) Use of mobile phone text
message reminders in health care services: a narrative literature review..
Journal of medical Internet research. 16(10): e222.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211035/
16 Marcano Belisario José S; Huckvale Kit, Greenfield Geva, Car Josip, Gunn
Laura H; (2013) Smartphone and tablet self management apps for asthma.
Cochrane Database of Systematic Reviews. (11): .
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010013.pub2/full
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17 Nieuwlaat Robby, Wilczynski Nancy, Navarro Tamara, Hobson Nicholas,
Jeffery Rebecca, Keepanasseril Arun, Agoritsas Thomas, Mistry Niraj, Iorio
Alfonso, Jack Susan, Sivaramalingam Bhairavi, Iserman Emma, Mustafa
Reem A; Jedraszewski Dawn, Cotoi Chris, Haynes R Brian; (2014)
Interventions for enhancing medication adherence. Cochrane Database of
Systematic Reviews. (11): .
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000011.pub4/abstract
18 Royal Pharmaceutical Society; (2013) Improving patient outcomes: The better
use of multi-compartment compliance aids. London: Royal Pharmaceutical
Society. http://www.rpharms.com/support-pdfs/rps-mca-july-2013.pdf
19 Ryan Rebecca, Santesso Nancy, Lowe Dianne, Hill Sophie, Grimshaw
Jeremy, Prictor Megan, Kaufman Caroline, Cowie Genevieve, Taylor Michael,
(2014) Interventions to improve safe and effective medicines use by
consumers: an overview of systematic reviews. Cochrane Database of
Systematic Reviews. (4): .
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007768.pub3/abstract
20 Tran N, Coffman JM, Sumino K, Cabana MD (2014) Patient reminder systems
and asthma medication adherence: a systematic review.. The Journal of
asthma : official journal of the Association for the Care of Asthma. 51(5): 536-
43.
http://informahealthcare.com/doi/abs/10.3109/02770903.2014.888572
21 Van Camp YP, Van Rompaey B, Elseviers MM (2013) Nurse-led interventions
to enhance adherence to chronic medication: systematic review and meta-
analysis of randomised controlled trials.. European journal of clinical
pharmacology. 69(4): 761-70.
http://link.springer.com/article/10.1007%2Fs00228-012-1419-y
22 Vervloet M, Linn AJ, van Weert JC, de Bakker DH, Bouvy ML, van Dijk L
(2012) The effectiveness of interventions using electronic reminders to
improve adherence to chronic medication: a systematic review of the
literature.. Journal of the American Medical Informatics Association : JAMIA.
19(5): 696-704.
http://jamia.oxfordjournals.org/content/19/5/696
23 Viswanathan M, Golin CE, Jones CD, Ashok M, Blalock S, Wines RC, Coker-
Schwimmer EJ, Grodensky CA, Rosen DL, Yuen A, Sista P, Lohr KN (2012)
Closing the quality gap: revisiting the state of the science (vol. 4: medication
adherence interventions: comparative effectiveness).. Evidence
report/technology assessment. (208.4): 1-685.
24 Wilson Hamish, Barber Nick (2013) Review of NHS pharmaceutical care of
patients in the community in Scotland. Edinburgh: Scottish Government.
http://www.gov.scot/Publications/2013/08/4406/0
18
Acknowledgements: We would like to thank staff at the EPPI-Centre, University
College London Institute of Education, for advice on the review process, report
summaries and EPPI-reviewer software support and training.
Date this summary was last updated: June 2015
Suggested citation for this evidence summary: Pharmaceutical care and
interventions to promote medicines adherence Unpublished review: NHS Education
for Scotland, Scotland
For further information please contact: [email protected]
19
Appendix 1 – Search Strategy
Cochrane Search
Cochrane Search 30/01/2015
Title or abstract
(complian* or adheren* or concordan*) AND (pharmacotherapy or medicat* or
"pharmaceutical care" or medi-dose or "dosette boxes")
Jan 2013-Feb 2015
46 results
Epistemonikos
Title or abstract
(complian* or adheren* or concordan*) AND (pharmacotherapy or medicat* or
"pharmaceutical care" or medi-dose or "dosette boxes")
Publication year: last 5 years (NB only had options to search for the last year or the
last 5 years)
Added to database 12 Jan 2013 to Feb 2015
Publication type: Systematic review
Systematic review question: ALL
Type of meta-analysis: ALL
Country or regional focus: blank (as UK gave no results)
232 results
Export facility only allowed to export for first 100 results as login required to export a
larger file
Health Systems Evidence
(complian* or adheren* or concordan*) AND (pharmacotherapy or medicat* or
"pharmaceutical care" or medi-dose or "dosette boxes")
70 results only displayed 50 of which 5 were relevant
NIHR
"medic* adherence", "medic* compliance", "medic* concordance" – 0
compliance or adherence or concordance – no results
20
National Guidelines Clearing House
Searched on medic* adherence, Compliance aids, compliance devices, medidose,
dosette boxes, pharmaceutical care, multi-compartment compliance aids, monitored
dosage systems.
Other Sources
Clinical Knowledge Summaries scanned and searched on medic* adherence.
Scottish Intercollegiate Guidelines Network (SIGN), National Institute for Health and
Care Excellence (NICE), Clinical Knowledge Summaries, the Royal Pharmaceutical
Society, General Pharmaceutical Council and Community Pharmacy Scotland all
scanned for relevant publications.
21
Appendix 2 Intervention: All interventions
Authors Authors’ comments on quality Review findings Nieuwlaat (2014) The author noted that many studies had a
high risk of bias. 17 studies had the lowest risk of bias for study design features. The RCTs at lowest risk of bias generally involved complex interventions with multiple components. Only five of these RCTs reported improvements in both adherence and clinical outcomes, and no common intervention characteristics were apparent.
• interventions were complex and required frequent interaction with the patient to focus on adherence
• insufficient evidence that newer intervention types e.g. mobile text messaging and internet-based care can improve adherence.
• methods to improve adherence need to be used for as long as the treatment is required.
Ryan (2014) High relevance non-Cochrane reviews were screened and excluded from the overview if the review was of low quality. Quality of included systematic reviews was assessed using the AMSTAR instrument.
• no single strategy improved all medicines-use outcomes across all diseases, populations or settings.
• Strategies that appear to improve medicines use include medicines self-monitoring and self-management programmes, dosing regimens and directly involving pharmacists in medicines management (eg medicines reviews)
• Strategies, including practical management tools (eg reminders, packaging) combined with other interventions may also have some positive effects, but their effects are less consistent.
• uncertainty remains about the effects of many interventions as there was not much evidence available for children and young people, carers, and people with multimorbidity.
Intervention: Multi-compartment compliance aids
Oboh, (2013) Guidelines
Review based on policy documents, guidelines rather than studies.
• Resource reviews use of MCAs for older people and provides case study examples and practical exercises.
• Advantages: reminder/prompt for patient to take their medicines is an attempt to simplify complex drug regimen
• Provides a way for carers & relatives to support person to take medicines themselves
• Disadvantages: only solid oral tablets; some drugs can't be put in MCA's as it interferes with effectiveness; there are safety issues drugs may need to be kept in special conditions (eg. temperature, light, moisture)
• drugs need to be taken according to instructions, which may not be available in box
• patients confusion about what they have taken
Royal Pharmaceutical Society (2013)
Reference is made to quality sources such as NICE guidelines and a Cochrane review. The authors found insufficient data evidence on the the effectiveness of the barrier properties of sealed MCA and the stability of medicines when stored outside of the manufacturer’s original packaging.
• insufficient evidence to support the benefits of MCA in improving medicines adherence in patients, or in improving patient outcomes insufficient data on the stability of medicines when stored outside of the manufacturer’s original packaging.
• Where multiple medicines are repackaged within a single MCA compartment, this can lead to the medicines interacting
• If other systems of medicines administration are required in addition to MCA (for example where the formulation or dosage of medicines are not suitable for inclusion within an MCA) this introduces complexity and potential confusion
•
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• use of MCA systems is associated with disadvantages in the supply of relevant necessary information
Intervention: Packaging interventions
Boeni (2014) Methodological quality was strong in 5 studies. Two studies provided complete information. Clear research gaps emerged- tool for quantitative studies developed for public health topics by the Effective Public Health Practice Project (EPHPP) group at conclusion says only 3 studies were graded as methodologically strong
• The methodological quality was considered low & firm conclusions about effects of the packaging could not be made
• The main research gaps concerned economic, disease-unspecific clinical outcomes and humanistic outcomes
• Future reviews should have more focus on patient safety & benefits to patients
Conn (2014) The author notes that the risk of bias was poorly reported in many of the primary studies. Some studies did not report whether intervention allocation was concealed and others did not report masking data collectors. Most studies randomly assigned subjects to treatment and control conditions but 14 did not.
• The meta-analysis findings supported the use of packaging interventions to effectively increase medication adherence.
• The study only included pill boxes and blister packs, not other packaging interventions
• There was evidence of publication bias, and primary study sparse reporting of health outcomes and potentially interesting moderating variables such as the number of prescribed medications.
Intervention: multi-media educational interventions
Ciciriello (2013) The author notes that findings were based on a small number of studies, many of which were of low quality- Five studies measured compliance or adherence to the prescribed medication.
• Compliance with medications: There is moderate quality evidence that there was no difference between multimedia education and usual care or no education
Intervention: dosing frequencies
Coleman (2012) The authors noted that some studies did not report blinding of patients in trials to the intervention (electronic monitoring device). All studies collected adherence data.
• Patients with chronic diseases appear to be more adherent with once-daily compared with more frequently scheduled medication regimens. The use of more precise definitions of adherence increased these findings.
Intervention: incentives DeFulio (2012) The authors applied strict exclusion
criteria: articles selected for inclusion in this review had to be peer reviewed empirical evaluations of incentives provided to patients contingent upon medication adherence. Studies in which the incentives were not described precisely or in which the incentives were not delivered by the study team or a service provider were excluded. Any studies that featured incentives in conjunction with other interventions for promoting medication adherence were excluded if they did not specifically evaluate the role of incentives.
• The review indicates that incentive-based medication adherence interventions could be very effective, but there were few controlled studies to provide evidence for this.
• The studies on incentive-based medication adherence interventions most commonly featured patients taking medication for drug or alcohol dependence, HIV, or latent tuberculosis.
• Cross-study comparisons indicated a positive relationship between the value of the incentive and the impact of the intervention. Post-intervention evaluations were rare, but tended to find that adherence effects diminish after the interventions are discontinued.
Intervention type: electronically compiled drug dosing histories/device dose memory functions
Demonceau (2013) The author mentions methodological weaknesses in the study designs and methods. As a result of the methodological differences, identifying interventions that could effectively enhance adherence to medications became more challenging.
• Evidence from the meta-analysis suggests that EM-feedback and cognitive-educational interventions are potentially effective approaches to enhance patient adherence to medications.
• The limitations of the research highlight the urgent need to define guidelines and study characteristics for research protocols that can guide researchers in designing studies to assess the effects of adherence-enhancing interventions. Review findings
23
Hall (2014) The author noted that the study designs differed.
• Devices with dose-memory and combined dose-memory and dose-reminder functions were found to improve self-reported and electronically monitored treatment adherence in chronic conditions such as asthma, diabetes, and HIV.
• The ability of the devices to provide dose-history information and active medication reminders was considered valuable in disease management by patients, caregivers, and healthcare professionals.
• The devices were found to enhance patients’ confidence in, and motivation to manage their medication and condition, and help reduce forgotten or incorrect medication dosing.
Intervention type: cognitive based behaviour change and counselling
Easthall (2013) The studies included in this meta-analysis were restricted to randomised controlled trials. Techniques to account for publication bias were used. Notable differences were reported when studies were combined, which the author thought could be a limitation.
• Cognitive based behaviour change therapies (CBCTs) were found to be effective interventions for improving medication adherence and capable of realising greater adherence rates than those achieved with educational and behavioural interventions.
• According to the results of the review’s subgroup analyses, CBCTs can be effectively delivered by routine healthcare providers.
• The review indicates that healthcare providers may wish to consider adopting these techniques in their medication adherence consultations.
Van Camp (2013) The author noted that the quality of the studies was of acceptable to high standard.
• Counselling appears to be an effective approach that nurses can use to supplement other methods
• Tackling non-adherence seems to demand continuous efforts and follow-up.
Intervention type: new technology Kannisto (2014) The authors state that their findings cannot
be used to recommend any preferred strategy for the use of mobile phone text message reminders in health care, as the analysis of data was done using a narrative method rather than meta-analysis. Studies differed in methodological quality.
• The review could not draw any firm conclusions but mobile phone text message reminders were found to have the potential to improve adherence to medication
• Further research is required using studies based on randomised controlled trials of effectiveness & cost-effectiveness.
• Research is also required to analyse user needs and preferences for text message reminders.
• The best ways to guarantee privacy and security when using mobile phone text message reminders has yet to be identified.
Review findings
24
Marcano (2013) Authors judged the evidence to have a GRADE rating of low quality.
• current evidence base is not sufficient to advise clinical practitioners, policy-makers and the general public with regards to the use of smartphone and tablet computer apps for the delivery of asthma self management programmes.
• future research should attempt to minimise the differences in clinical management of patients between control and intervention groups
• studies evaluating apps as part of complex, multicomponent interventions, should analyse each part of the intervention separately researchers should take into account the seasonal nature of asthma and long-term adherence to self management practices.