Medication Safety in Polypharmacy - Technical Report - World Health Organization

 
Medication Safety in Polypharmacy - Technical Report - World Health Organization
Medication Safety in
     Polypharmacy

      Technical Report
Medication Safety in
     Polypharmacy

      Technical Report
WHO/UHC/SDS/2019.11

© World Health Organization 2019

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Contents

Abbreviations .................................................................................................................................... 4
Preface .............................................................................................................................................. 5
Executive summary: medication safety in polypharmacy ............................................................ 10
1. Introduction.................................................................................................................................. 11
   1.1 Polypharmacy .......................................................................................................................... 11
   1.2 Prevalence of polypharmacy .................................................................................................. 12
   1.3 Economic impact of polypharmacy ........................................................................................ 13
   1.4 Other factors influencing appropriate polypharmacy.............................................................. 14
2. Medication safety in polypharmacy .......................................................................................... 15
   2.1 Medication-related harm in polypharmacy.............................................................................. 15
   2.2 Medication review in polypharmacy ...................................................................................... 16
3. Implementing polypharmacy initiatives .................................................................................... 20
   3.1 Implementing sustainable programmes to address polypharmacy........................................ 20
   3.2 Programmes on appropriate polypharmacy .......................................................................... 21
4. Health systems approach to polypharmacy .............................................................................. 23
   4.1 Patients and the public............................................................................................................ 24
   4.2 Health care professionals ...................................................................................................... 25
   4.3 Medicines................................................................................................................................ 25
   4.4 Systems and practices of medication .................................................................................... 26
   4.5 Monitoring and evaluation ...................................................................................................... 27
5. Points of consideration for countries ........................................................................................ 29
References ...................................................................................................................................... 30
Annexes .......................................................................................................................................... 38
Annex 1. Glossary ............................................................................................................................ 38
         Glossary references .......................................................................................................... 41
Annex 2. Global prevalence of polypharmacy ................................................................................ 43
Annex 3. Internationally available guidance on appropriate polypharmacy management .............. 47
Annex 4. Case studies .................................................................................................................... 49
Annex 5. List of contributors ............................................................................................................ 59

                                                                                                  MEDICATION SAFETY IN POLYPHARMACY                        3
Abbreviations

    ACE               angiotensin-converting enzyme
    ADR               adverse drug reaction
    ARB               angiotensin II receptor blocker
    BP                blood pressure
    COPD              chronic obstructive pulmonary disease
    eGFR              estimated glomerular filtration rate
    NNH               number needed to harm
    NNT               number needed to treat
    NSAID             non-steroidal anti-inflammatory drug
    OTC               over-the-counter
    PESTEL            political, economic, social, technological, environmental and legal
    PIM               potentially inappropriate medication
    RLS               reporting and learning systems
    SWOT              strengths, weaknesses, opportunities and threats
    UHC               universal health coverage
    WHO               World Health Organization

4    MEDICATION SAFETY IN POLYPHARMACY
Preface

Health care interventions are intended to          prescribed, dispensed or sold inappropriately,
benefit patients, but they can also cause          with many of these leading to preventable harm
harm. The complex combination of processes,        (2). Given that medicines are the most common
technologies and human interactions that           therapeutic intervention, ensuring safe
constitutes the modern health care delivery        medication use and having the processes in
system can bring significant benefits.             place to improve medication safety (see Annex
However, it also involves an inevitable risk of    1) should be considered of central importance
patient harm that can – and too often does –       to countries working towards achieving UHC.
result in actual harm. A weak safety and
quality culture, flawed processes of care          The Global Patient Safety Challenges of the
and disinterested leadership teams weaken          World Health Organization (WHO) shine a light
the ability of health care systems and             on a particular patient safety issue that poses a
organizations to ensure the provision of safe      significant risk to health. Front-line interventions
health care. Every year, a significant number      are then developed and, through partnership
of patients are harmed or die because of           with Member States, are disseminated and
unsafe health care, resulting in a high public     implemented in countries. Each Challenge has
health burden worldwide.                           so far focused on an area that represents a
                                                   major and significant risk to patient health and
Most of this harm is preventable. Adverse          safety (see Annex 1). In 2005, the Organization,
events are now estimated to be the 14th leading    working in partnership with the (then) World
cause of morbidity and mortality in the world,     Alliance for Patient Safety, launched the first
putting patient harm in the same league as         Global Patient Safety Challenge: Clean Care Is
tuberculosis and malaria (1). The most important   Safer Care (3), followed a few years later by the
challenge in the field of patient safety (see      second Challenge: Safe Surgery Saves Lives
Annex 1) is how to prevent harm, particularly      (4). Both Challenges aimed to gain worldwide
avoidable harm, to patients during their care.     commitment and spark action to reduce health
                                                   care-associated infection and the risks
Patient safety is one of the most important        associated with surgery, respectively.
components of health care delivery which is
essential to achieve universal health coverage     Recognizing the scale of avoidable harm
(UHC), and moving towards the UN Sustainable       linked with unsafe medication practices and
Development Goals (SDGs). Extending health         medication errors, WHO launched its third
care coverage must mean extending safe care,       Global Patient Safety Challenge: Medication
as unsafe care increase costs, reduces             Without Harm in March 2017, with the goal
efficiency, and directly compromises health        of reducing severe, avoidable medication-
outcomes and patient perceptions. It is            related harm by 50% over the next five years,
estimated that over half of all medicines are      globally (5).

                                                                MEDICATION SAFETY IN POLYPHARMACY         5
This Challenge follows the same philosophy as      and effective management to protect patients
    the previous Challenges, namely that errors are    from harm while maximizing the benefit from
    not inevitable, but are very often provoked by     medication, namely:
    weak health systems, and so the challenge is to    • medication safety in high-risk situations
    reduce their frequency and impact by tackling      • medication safety in polypharmacy
    some of the inherent weaknesses in the system.     • medication safety in transitions of care.

    As part of the Challenge, WHO has asked            Consider the following case scenario
    countries and key stakeholders to prioritize       describing a medication error (see Annex 1)
    three areas for strong commitment, early action    involving these three areas.

     Medication error: case scenario
     Mrs Poly, a 65-year-old woman, came to the outpatient clinic complaining of abdominal pain and
     dark stools. She had a heart attack five years ago. At her previous visit three weeks ago she was
     complaining of muscle pain, which she developed while working on her farm. She was given a
     non-steroidal anti-inflammatory drug (NSAID), diclofenac. Her other medications included aspirin,
     and three medicines for her heart condition (simvastatin, a medicine to reduce her serum
     cholesterol; enalapril, an angiotensin-converting enzyme (ACE) inhibitor; and atenolol, a beta
     blocker). She was admitted to hospital as she developed symptoms of blood loss (such as
     fatigue and dark stools). She was provisionally diagnosed as having a bleeding peptic ulcer due
     to her NSAID, and her doctor discontinued diclofenac and prescribed omeprazole, a proton
     pump inhibitor. Following her discharge, her son collected her prescribed medicines from the
     pharmacy. Among the medicines, he noticed that omeprazole had been started and that all her
     previous medicines had been dispensed, including the NSAID. As his mother was slightly
     confused and could not remember exactly what the doctor had said, the son advised his mother
     that she should take all the medications that had been supplied. After a week, her abdominal
     pain continued and her son took her to the hospital. The clinic confirmed that the NSAID, which
     should have been discontinued (deprescribed), had been continued by mistake. This time Mrs
     Poly was given a medication list when she left the hospital which included all the medications
     she needed to take and was advised about which medications had been discontinued and why.

6    MEDICATION SAFETY IN POLYPHARMACY
The events leading to the error in this scenario and how these could have been prevented are
reflected in Figure 1, and the text below.

Figure 1. Key steps for ensuring medication safety

                                                                        1.
                                                                        Appropriate
                                                                        prescribing
                                                                        and risk
                                                                        assessment
                    5.
         Medication                                            Risks
       reconciliation                                Benefit
  at care transitions

                                                                                         2.
                                                                                         Medication
                                                                                         review

                                                                       3.
                4.                                                     Dispensing,
                Communication                                          preparation and
                and patient engagement                                 administration

In this scenario the key steps that should have      2. Medication review
been followed to ensure medication safety            A comprehensive medication review (see
in the inpatient setting include:                    Annex 1) is a multidisciplinary activity whereby
                                                     the risks and benefits of each medicine are
1. Appropriate prescribing and risk                  considered with the patient and decisions
assessment                                           made about future therapy. It optimizes the use
Medication safety should start with appropriate      of medicines for each individual patient.
prescribing and a thorough risk–benefit              Multiple morbidities usually require treatment
analysis of each medicine is often the first step.   with multiple medications, a situation described
In this case scenario, prophylactic aspirin          as polypharmacy (see Annex 1). Polypharmacy
and NSAID without a gastroprotective agent           can put the patient at risk of adverse drug
left Mrs Poly at an increased risk of                events (see Annex 1) and drug interactions
gastrointestinal bleeding. NSAIDs can also           when not used appropriately. In this case,
increase the risk of cardiovascular events,          there should have been a review of
which is of particular concern, as she had had       medications, particularly as Mrs Poly was
a myocardial infarction (heart attack) five years    prescribed aspirin and diclofenac together.
ago. This is a good example of a high-risk           The haemodynamic changes following blood
situation requiring health care professionals        loss should have also prompted temporary
to prescribe responsibly after analysing             stopping the ACE inhibitor before restarting once
the risks and benefits.                              the episode of blood loss has been resolved.

                                                                  MEDICATION SAFETY IN POLYPHARMACY      7
3. Dispensing, preparation and                          5. Medication reconciliation at care
    administration                                          transitions
    This is a high-risk situation as the medication         Medication reconciliation is the formal process
    (diclofenac) has the potential to cause harm.           in which health care professionals partner
    However, this medication was continued after            with patients to ensure accurate and complete
    discharge when the patient transitioned from            medication information transfer at interfaces
    hospital to home. Dispensing this medicine and its      of care. Diclofenac, the NSAID that can cause
    administration caused serious harm to Mrs Poly.         gastrointestinal bleeding and increase the risk
    Dispensing this medicine and its administration         of cardiotoxicity and had led to this hospital
    caused significant harm to Mrs Poly.                    admission, was discontinued, and this
                                                            information should have been communicated
    4. Communication and patient engagement                 at the time of discharge (in the form of a
    Proper communication between health care                medication list or patient-held medication
    providers and patients, and amongst health              record). This would have helped her and her
    care providers, is important in preventing              caregivers in determining what the newly added
    errors. When Mrs Poly was severely ill due to           and discontinued medications needed to be.
    gastric bleeding, the NSAID was discontinued.
    However, the decision to discontinue the                Medication-related harm is harm caused to
    medicine was not adequately communicated                a patient due to failure in any of the various
    either to the other health care professionals           steps of the medication use process or due
    (including the nurse or the pharmacist) or to           to adverse drug reactions (see Annex 1 for
    Mrs Poly. Initial presenting symptoms due to            glossary). The relationship and overlap between
    adverse effects could have been identified              medication errors and adverse drug events
    earlier if she had been warned about the risks.         is shown in Figure 2.

    Figure 2. Relationship between medication errors and adverse drug events

                 Adverse drug events

                           Injury                                            No injury
                                                                                                        Outcomes

            Adverse                  Preventable               Potential                   Trivial
             drug                   adverse drug             adverse drug                medication
           reactions                   events                   events                     errors
                                                                                                        Causes

         Not preventable                                       Preventable

           Inherent risk                                   Medication errors
             of drugs

    Source: Reproduced, with the permission of the publisher, from Otero and Schmitt (6).

8    MEDICATION SAFETY IN POLYPHARMACY
WHO is presenting a set of three technical          This report – Medication safety in
reports – Medication safety in high-risk            polypharmacy – outlines the problem, current
situations, Medication safety in polypharmacy,      situation and key strategies to reduce
and Medication safety in transitions of care –      medication-related harm in polypharmacy.
to facilitate early priority actions and planning   It should be considered along with the
by countries and key stakeholders to address        companion technical reports on Medication
each of these areas. The technical reports are      safety in high-risk situations and Medication
intended for all interested parties, particularly   safety in transitions of care.
to inform national health policy-makers and
encourage appropriate action by ministries
of health, health care administrators and
regulators, organizations, professionals,
patients, families and caregivers, and all who
aim to improve health care and patient safety.

                                                                MEDICATION SAFETY IN POLYPHARMACY   9
Executive summary:
                        medication safety
                        in polypharmacy

     Ensuring medication safety in polypharmacy        and/or services may be necessary to help
     is one of the key challenges for medication       medical practitioners manage workload
     safety today. Due to the traditional focus        related to polypharmacy in order to improve
     of both medical research and health care          medication safety.
     delivery models on single-disease
     interventions, there has been a notable lack      In complex health care setting with many
     of evidence-based solutions. Conventionally       competing priorities, it is useful to outline
     polypharmacy has been perceived as an             the safety, clinical and economic implications
     overuse of medicines, whereas it may be more      for appropriate polypharmacy management.
     useful to perceive in terms of appropriateness,   It can also be helpful to develop an
     as there are many cases where the concurrent      implementation plan which applies change
     use of multiple medicines may be deemed           management and implementation theories
     necessary and beneficial. Globally the            and tools. The four domains in the strategic
     prevalence of polypharmacy is set to rise as      framework of the third WHO Global Patient
     the population ages and more people suffer        Safety Challenge: Medication Without Harm
     from multiple long-term conditions. Countries     can assist in providing a guiding structure
     should therefore prioritize raising awareness     to create a medication safety strategy
     of the problems associated with inappropriate     addressing polypharmacy.
     polypharmacy and the need to address this
     issue.

     All stakeholders have a vital role to play
     in driving change for the management
     of polypharmacy. Polypharmacy management
     involves multifaceted decision-making and
     necessitates the combined knowledge of
     physicians, nurses, pharmacists and other
     health care professionals, including the
     systematic involvement, engagement and
     empowerment of patients. Thus it is important
     to implement interventions, such as medication
     reviews, whenever possible in collaboration
     with the patient and/or the caregiver. Good
     communication and accurate sharing of
     information is essential and can be facilitated
     by the use of patient-held medication records.
     Furthermore, a redesign of care processes

10    MEDICATION SAFETY IN POLYPHARMACY
Introduction
                                                                                              1
This technical report does not attempt                Polypharmacy is the concurrent use
to cover the entire scope of polypharmacy,            of multiple medications. Although there
but merely aims to introduce polypharmacy             is no standard definition, polypharmacy
as a concept, and examine some approaches             is often defined as the routine use of five
for the appropriate management of                     or more medications. This includes
polypharmacy, which are crucial for ensuring          over-the-counter, prescription and/or
greater medication safety.                            traditional and complementary medicines
                                                      used by a patient (see Annex 1).
1.1 Polypharmacy

Despite the increasing prevalence                   While polypharmacy is often defined as
of polypharmacy, the term continues to lack         routinely taking a minimum of five medicines,
a clear universal definition. A recent systematic   it is being more frequently suggested that
review of the definitions of polypharmacy           the emphasis should be on evidenced-based
showed that the term was most commonly              practice (7). The goal should be to reduce
applied to situations where patients took five      inappropriate polypharmacy (irrational
or more medications, and this numerical             prescribing of too many medicines)
definition was used by 46.4% of the studies         and to ensure appropriate polypharmacy
evaluated (7). Furthermore, there are               (rational prescribing of multiple medicines
inconsistencies with the use regarding              based on best available evidence and
duration of therapy and whether to include          considering individual patient factors and
over-the-counter (OTC), and traditional and         context) (7–11). Therefore, appropriate
complementary medicines in the definition           polypharmacy should be considered at every
or not. However, with the aim of reducing           point of initiation of a new treatment for the
medication-related harm, it is important            patient, and when the patient moves across
to verify to the fullest extent possible all        different health care settings.
the medications that the patient is taking,
including all OTC, and traditional and
complementary medicines.

                                                                MEDICATION SAFETY IN POLYPHARMACY    11
Appropriate polypharmacy is present, when (a) all medicines are prescribed for the purpose of
       achieving specific therapeutic objectives that have been agreed with the patient; (b) therapeutic
       objectives are actually being achieved or there is a reasonable chance they will be achieved in
       the future; (c) medication therapy has been optimized to minimize the risk of adverse drug
       reactions (ADRs); and (d) the patient is motivated and able to take all medicines as intended (12).
       Inappropriate polypharmacy is present, when one or more medicines are prescribed that are
       not or no longer needed, either because: (a) there is no evidence based indication, the indication
       has expired or the dose is unnecessarily high; (b) one or more medicines fail to achieve the
       therapeutic objectives they are intended to achieve; (c) one, or the combination of several
       medicines cause ADRs, or put the patient at a high risk of ADRs or because (d) the patient is not
       willing or able to take one or more medicines as intended (12).

     Polypharmacy has been described as                   1.2 Prevalence of polypharmacy
     a significant public health challenge (13).
     It increases the likelihood of adverse effects,      Polypharmacy is a major and growing public
     with a significant impact on health outcomes         health issue occurring within all health care
     and expenditure on health care resources             settings worldwide (8, 13). The issue is well
     (14–16). Although co-prescribing multiple            described in literature from countries in North
     medicines increases the risk of adverse events,      America (10, 18), Europe (8, 22) and the
     it is important to note that assigning a numeric     Western Pacific (23), with more data becoming
     threshold to define polypharmacy is not always       available from other countries in recent years.
     useful. There are cases where polypharmacy           Additional information from selected countries
     is necessary and beneficial, such as the             is available in Annex 2, illustrating that
     secondary prevention of myocardial infarction,       polypharmacy is a global problem. However,
     which requires the use of four different classes     variation in the structure of health care delivery
     of medications (a beta blocker, a statin, an         and data collection systems, compounded
     antiplatelet agent and an ACE inhibitor) (8, 12).    by the different operational definitions of
     Appropriate polypharmacy recognizes that             polypharmacy, makes country comparison
     patients can benefit from multiple medications       difficult.
     if the patients’ clinical conditions,
     comorbidities, allergy profiles, the potential         Multimorbidity is defined as the presence
     drug–drug and drug–disease interactions                of two or more long-term health conditions,
     are considered, and the medicines are                  which can include (a) defined physical and
     prescribed based on the best available                 mental health conditions such as diabetes
     evidence (17). Thus, it is critical to distinguish     or schizophrenia; (b) ongoing conditions
     appropriate polypharmacy from inappropriate            such as learning disability; (c) symptom
     polypharmacy (12).                                     complexes such as frailty or chronic pain;
                                                            (d) sensory impairment such as sight or
     The most vulnerable patient groups to the risks        hearing loss; and (e) alcohol and substance
     of polypharmacy are susceptible to events              misuse (see Annex 1).
     such as drug–drug interactions, higher risk
     of falls, ADRs, cognitive impairment,
     non-adherence and poor nutritional status            While its true magnitude is not known,
     (18–20). Vulnerable patient groups often             the prevalence of polypharmacy is expected
     include older patients above the age of              to rise due to a multitude of factors (8). First,
     65 years and patients who are living in care         the global population faces a demographic
     homes (19–21).                                       shift with the proportion of older population

12    MEDICATION SAFETY IN POLYPHARMACY
groups on the rise. It has been estimated             1.3 Economic impact
that the global population aged over 65 years         of polypharmacy
will double from 8% in 2010 to 16% in 2050
(24). In 2015, approximately 5% of the                Advancing the responsible use of medicines:
population in OECD countries were aged                applying levers for change identified several
80 years and above, this percentage is                opportunities to reduce health care spending
expected to rise more than double by 2050             through more responsible use of medicines
(25). Second, epidemiological data indicates          worldwide. The authors estimated that
that multimorbidity increases markedly                mismanaged polypharmacy contributed to 4%
with age. In a Scottish study, multimorbidity         of the world’s total avoidable costs due
was prevalent in 81.5% of individuals aged            to suboptimal medicine use. A total of US$ 18
85 years and over, with a mean number of 3.62         billion, 0.3% of the global total health
morbidities (26). Ornstein et al. found that the      expenditure could be avoided by appropriate
most prevalent chronic conditions in primary          polypharmacy management. Some of the
care were hypertension (33.5%), hyperlipidemia        specific recommendations outlined in the
(33.0%), and depression (18.7%) (27). The             report included (33):
presence of multiple morbidities is associated        • investment in medical audits targeting older
with multiple symptoms, impairments and                 patients with multiple medications;
disabilities. Multimorbidity may result in            • support for a greater role of pharmacists in
a combined negative effect on physical                  medication management and in collaboration
and mental health, and can have a major                 with health care professionals for review
impact on a person’s quality of life, limiting          of therapeutic plans;
daily activities and reducing mobility (28, 29).      • identification of high-risk patients and
The need to take multiple medications can be            preparation of targeted medicine
just as problematic, resulting in frequent health       management plans for this group; and
care contacts and an increase in the likelihood       • to establish a system for blame-free reporting
of medication-related harm (30). Furthermore,           of medication errors.
it imposes a large economic burden due
to patients’ complexity of health care needs          The objectives of polypharmacy management
and frequent interaction with health services,        should be comprehensive, addressing such
which may be fragmented, ineffective and              issues as improved health outcomes for
incomplete (31).                                      the patient and population, greater patient
                                                      engagement in therapeutic decision-making
Despite extensive advances in                         and cost-effectiveness of health care systems
pharmacotherapy, the availability of clinical         and resources. This comprehensive approach –
guidelines for older adults with multiple             embracing care, health and cost – has been
morbidities is limited (28). Prescribing is largely   termed the “triple aim” strategy, and it is
based on evidence-based guidance for single           designed to guide health system performance
diseases, which does not generally take into          optimization (34). The term has been built
account multimorbidity (21, 28, 32).                  upon to become a “quadruple aim” upon
Consequently, patients are often prescribed           recognizing that staff wellbeing is essential
several medicines recommended by a number             to ensure good care for the public (35).
of specialists using disease-specific guidelines
which in combination makes the management             Improved safety and quality leading
of any single disease challenging and may             to economic benefits
even lead to patient harm (21, 26).                   In a randomized control trial by Gillespie et al.
                                                      clinical pharmacists performed comprehensive
                                                      medication reviews (see Annex 1) of older
                                                      hospitalized patients. Patients that received

                                                                   MEDICATION SAFETY IN POLYPHARMACY      13
a medication review experienced 16%                1.4 Other factors influencing
     fewer hospital visits and 47% fewer visits         appropriate polypharmacy
     to the emergency department within a 12-
     month follow-up period, compared to those          Social determinants of health and lifestyles
     with usual care. In addition, medication-related   A proactive approach to sustainable and
     readmissions were reduced by 80%. After            appropriate medication regimens should target
     factoring in the intervention costs, the           lifestyles as part of the health management
     comprehensive medication reviews were found        process. It is recognized that an unhealthy
     to lower the total hospital-based health care      lifestyle can contribute to multimorbidity,
     cost per patient by US$ 230. The conclusion        requiring treatment with multiple medications
     presumed that the addition of clinical             (37). Unhealthy lifestyle factors should be
     pharmacists to health care teams on a wider        discussed with patients when considering
     scale could result in even greater health care     alternatives to medication. The WHO Active
     cost reductions and reducing morbidity (36).       ageing: a policy framework identified three
                                                        important economic factors for active ageing:
                                                        income, work and social protection (38).
                                                        Individuals with low incomes may be restricted
                                                        in their choice of healthy ageing options as
                                                        healthy foods, health care and housing may be
                                                        less affordable and accessible, and are thus
                                                        at higher risk of ill health and disability (39),
                                                        which can be exacerbated for patients with
                                                        polypharmacy.

                                                        Non-adherence
                                                        Non-adherence to prescribed medication is
                                                        a major challenge in polypharmacy, particularly
                                                        among older persons and/or in patients with
                                                        multimorbidity. Older patients who receive
                                                        treatment for several chronic health conditions
                                                        simultaneously present both pharmacological
                                                        and medication adherence (see Annex 1) risks
                                                        (40). A systematic review of older patients with
                                                        polypharmacy found a correlation between
                                                        medication non-adherence and the number
                                                        of medicines being taken (41).

14    MEDICATION SAFETY IN POLYPHARMACY
Medication safety
                               in polypharmacy
                                                                                              2
This section outlines the case for managing        Learning from medication incidents is vital
polypharmacy at the point of initiation of         for the implementation of preventive strategies
treatment, when prescribing, when adding           and interventions in order to reduce risk and
a new medication to a patient’s list of            prevent harm from occurring again (46).
medications, during a medication review, or
during a medication reconciliation (see Annex 1)   Polypharmacy at transitions of care
when a patient moves across care settings.         When patients move across care settings,
                                                   medication reconciliation is an important issue
2.1 Medication-related harm                        that needs to be addressed. A systematic
in polypharmacy                                    review of hospital based medication
                                                   reconciliation practices showed a consistent
Studies conducted in many countries have           reduction in medication discrepancies (see
estimated the rate of medication errors both       Annex 1), potential adverse effects and adverse
in hospitals and in general practice (42–45).      drug events after medication reconciliation,
One study by Avery et al. found that over a        with the most success seen in high-risk patient
12-month period, patients receiving five or more   populations such as polypharmacy patients
medications had a prescribing or monitoring        (50). Discrepancies in medication orders are
error rate of 30.1%, while in those receiving      common, and they increase with the number
10 or more medications the error rate was 47%,     of medications prescribed (51). A study of
demonstrating that the error rate increased        post-discharge patients found that almost one
with the number of medicines prescribed (42).      fifth of currently used prescription medicines
Another study conducted across eight               had not been recorded during hospitalization
countries found that the incidence of patient-     and that less than half of the medications used
reported errors increased with the number          had been registered in the patients’ discharge
of medications that were taken (43).               letter. This illustrates the challenge that health
                                                   care professionals encounter at transitions
Reporting of medication incidents such as          of care (see Annex 1), as polypharmacy in
medication errors and ADRs associated with         combination with an insufficient knowledge of
polypharmacy could provide useful information      the patients’ medication history is an important
to improve patient safety (46). Polypharmacy       contributor to prescribing errors, which can
may have harmful implications for patients         potentially result in adverse drug events (52).
such as an increased risk of medication errors,
drug–drug interactions, suboptimal patient         Polypharmacy in care homes
adherence and reduced quality of life (8, 47,      Residents of care homes may be at higher
48). Health care professionals together with       risk of complications from polypharmacy and
patients and caregivers play a crucial role in     inappropriate prescribing (21). Findings suggest
reporting medication-related events (46, 49).      that up to 40% of prescriptions for nursing

                                                                MEDICATION SAFETY IN POLYPHARMACY       15
home residents may be inappropriate or             2.2 Medication review
     suboptimal (53). Barber et al. found that          in polypharmacy
     the average care home resident in England
     was taking eight medications a day and               Medication review is a structured
     over two thirds of these residents had one           evaluation of patient’s medicines with
     or more medication errors (54). Inappropriate        the aim of optimizing medicines use and
     prescribing contributes toward the medication        improving health outcomes. This entails
     burden and exacerbates the problem of                detecting drug related problems and
     inappropriate polypharmacy. This is particularly     recommending interventions (see Annex 1).
     evident with regards to the widespread
     prescribing of antipsychotic medications           Medication reviews are widely used to address
     in patients with dementia in nursing and           inappropriate polypharmacy globally and are
     residential homes (55).                            also recommended by many polypharmacy
                                                        guidance documents, see Annex 3. It provides
     Non-prescribed medications                         a structured evaluation that can be used to
     In addition to prescribed medications, many        prevent harm, optimize treatments and improve
     patients self-medicate by purchasing OTC           outcomes by optimizing the use of medicines
     medicines. OTC medicines, such as NSAIDs           for each individual patient (8, 61). Medication
     for pain and some medications for allergies        reviews in polypharmacy should take into
     and coughs, may interact with their prescribed     account the effectiveness and the risk–benefit
     medications and have the potential to cause        ratio of the medication treatment options, and
     harm. In some cases, patients may also be          examine these criteria for the specific patient
     sharing prescription medicine with other           group in which the medication is being used.
     individuals (8, 56). Therefore it is important     Where possible medication reviews should be
     to carefully ask patients about the use            performed in collaboration with the patient or
     of all types of medicines or remedies (8).         their caregiver (8, 13).

     Traditional and complementary medicines            The main purpose of medication reviews is to
     The use of herbal medicines is widespread          improve the appropriateness of medications,
     and often taken in combination with                reduce harm and improve outcomes. Therefore,
     conventional medicines to treat diseases           it is essential to reassure that the review is not
     (49, 57, 58). Health care providers should         viewed merely as a mechanism to reduce
     ask their patients if they use traditional and     or stop medications.
     complementary medicines or remedies
     and include these products in the medication       A systematic review and meta-analysis
     review, as these will contribute to the            indicated that pharmacist-led medication
     polypharmacy burden (8). Alongside drug–drug       reviews led to a reduction in hospital
     interactions, herb–drug interactions should be     admissions (62). In addition, medication
     considered, as they can cause a considerable       reviews may have an effect on the reduction
     patient safety risk (49, 59, 60). Further          of medication-related problems (63, 64).
     high-quality research is needed to identify        For example, a study by Schnipper et al.
     interactions of herbal medicines (60).             found that medication reviews reduced
                                                        the number of preventable adverse drug
                                                        events 30 days after patient discharge (64).
                                                        One Cochrane review found that medication
                                                        reviews may have a preventive effect on
                                                        reducing the number of emergency
                                                        department contacts, however it did not
                                                        reduce mortality or hospital readmissions.

16    MEDICATION SAFETY IN POLYPHARMACY
The reducing effect on emergency department        considered for individual patients during the
visits was more significant in high-risk groups    decision making process. In polypharmacy
(such as older persons or patients with multiple   this ratio may vary considerably between
medications) (65). The general consensus           patients (61). For several commonly used
is that more evidence is necessary to              medications, there are some NNT and NNH
determine the effect of medication reviews         estimates available (61, 71).
due to the heterogeneity of the studies and
limitations in follow-up time (62, 66, 67).        Ideally, such information on risks and benefits
                                                   is made accessible and comprehensible
Assessing risks and benefits                       for the public, in order to include patients in
To facilitate the medication review, prescribers   the decision-making process. For example,
need practical tools and information to help       a Scottish polypharmacy guidance tool helps
with decision-making on the safety and             health care professionals work in partnership
effectiveness of medicines and the                 with patients. This resource is available as
appropriateness of initiating or continuing long   a combined mobile application and website
term medications (11). One useful measure          that outlines the process for initiation and
which helps prescribers to understand the          the review of treatments (72).
probable clinical efficacy of a medicine
is the number needed to treat (NNT). The NNT       Medication review process in polypharmacy
can be defined as the average number of            The review process should include
patients who require to be treated over a time     engagement with the patient. The perspective
period for one patient to benefit compared         of the patient on managing and taking multiple
with a control; it can also be expressed as the    medications should be assessed, as well
reciprocal of the absolute risk reduction (61).    as the patient’s goal of care. The intentions
The ideal NNT, being one, signifies that every     of the patient would need to be aligned with
patient improves on the outcome with the           the prescribers’ view of improving outcomes
treatment. The higher the NNT, the less            and treatment goals (8). The information and
effective the treatment is in terms of the trial   changes derived from the medication review
outcome and timescale. The NNT is only             should be made available to other health care
a statistical estimate of the average benefit of   professionals, especially as the patient
treatment, usually calculated based on clinical    moves across different care settings, in order
trials. It is rarely possible to know precisely    to enable collaboration in appropriate
the likely benefit for a particular patient.       polypharmacy management. An example
However, NNT still remains a universal concept     of a step-by-step method to conduct
to assess the efficacy of medicine. Several        a medication review while using a patient-
tables and further information are available on    centered approach is elaborated in Table 1.
NNT, which can support prescribers in decision     Annex 4 outlines how this process can be
making and aid discussions with patients           further applied to selected clinical scenarios.
regarding the potential benefits of their
treatment (61, 68–71).

Similarly to NNT, another measure used in
decision making is the Number Needed to
Harm (NNH). The NNH is the average number
of people taking a medication over a time
period in order for one adverse event to occur
(61). This concept is not as widely used as
the NNT. Combined with NNT, the overall
benefit to risk ratio (NNT/NNH) should be

                                                               MEDICATION SAFETY IN POLYPHARMACY     17
Table 1. Step-by-step approach to conducting a patient-centred medication review
     Aims           1. What matters       Review diagnoses and identify therapeutic objectives with
                       to the patient     respect to:
                                          • Understanding of goals of medication therapy
                                          • Management of existing health problems
                                          • Prevention of future health problems
     Need           2. Identify           Identify essential medications (not to be stopped without
                       essential          specialist advice) such as:
                       medications        • Medications that have essential replacement functions
                                            (e.g. thyroxine)
                                          • Medications to prevent rapid symptomatic decline
                                            (e.g. medications for Parkinson’s disease)
                    3. Does the           Identify and review the (continued) need for medications:
                       patient take       • With temporary indications
                       unnecessary        • With higher-than-usual maintenance doses
                       medications?       • With limited benefit in general for the indication they are used
                                            for
                                          • With limited benefit for the particular patient under review
     Effectiveness 4. Are                 Identify the need for adding/intensifying medication therapy
                      therapeutic         in order to achieve therapeutic objectives:
                      objectives          • To achieve symptom control
                      being               • To achieve biochemical/clinical targets
                      achieved?           • To prevent disease progression/exacerbation
     Safety         5. Does the           Identify patient safety risks by checking for:
                       patient have/      • Drug–disease interactions
                       is at risk of      • Drug–drug interactions
                       adverse drug       • Robustness of monitoring mechanisms for high-risk
                       reactions?           medications
                                          • Risk of accidental overdosing
                       Does the           Identify adverse drug effects by checking for:
                       patient know       • Specific symptoms/laboratory markers (e.g. hypokalaemia)
                       what to do if      • Cumulative adverse drug effects
                       they are ill?      • Medications that may be used to treat adverse drug
                                            reactions caused by other medications
     Costs          6. Is therapy      Identify unnecessarily costly medication by:
                       cost-effective? • Considering more cost-effective alternatives (but balance
                                         against effectiveness, safety, convenience)
     Patient-     7. Is the patient       Does the patient understand the outcomes of the review?
     centeredness    willing and          • Does the patient understand why they need to take their
                     able to take           medication?
                     medication           • Consider teach-back techniquea to ensure full understanding
                     as intended?         Ensure medication changes are tailored to patient preferences:
                                          • Is the medication in a form the patient can take?
                                          • Is the dosing schedule convenient?
                                          • Consider what assistance the patient might have and when
                                            this is available
                                          • Is the patient able to take medicines as intended?
                                          Agree and communicate plan:
                                          • Discuss with the patient therapeutic objectives and
                                            treatment priorities
                                          • Decide with the patient what medicines have an effect of
                                            sufficient magnitude to consider continuation or discontinuation
                                          • Inform relevant health care and social care change
                                            in treatments across care transitions

18    MEDICATION SAFETY IN POLYPHARMACY
a Method to confirm that the information provided is being understood by getting people to ‘teach-back’
 what has been discussed and what instruction has been given (73).
Source: Adapted, with permission of the publisher, from Scottish Government Polypharmacy Model
of Care Group (61).

  Deprescribing is the process of tapering,             criteria can be useful in deprescribing and
  stopping, discontinuing, or withdrawing               improving appropriate prescribing (72, 75).
  drugs, with the goal of managing                      Examples of prescribing indicator sets
  polypharmacy and improving outcomes                   which can be used to identify inappropriate
  (see Annex 1).                                        polypharmacy and appropriateness of
                                                        prescribing are available (8, 76). There are
Considerations for cessation of medication              also algorithms available that could improve
should be a part of all medication reviews,             medication therapy by deprescribing, which
and the process of “deprescribing” should be            have been shown to be feasible (77). Hence
as robust as that of prescribing. The process           it is important to undertake medication reviews
encompasses minimization of the medication              with a holistic approach, as medications may
load in terms of dosage, number of tablets              need to be started or stopped, both to prevent
taken and frequency of administration times             harm from some medications and to prevent
(23, 74). Supporting tools such as STOPP/START          health deterioration (8).

                                                                      MEDICATION SAFETY IN POLYPHARMACY   19
Implementing polypharmacy

3                        initiatives

     In order to address inappropriate polypharmacy      that can be applied across the entire health
     multiple programmes have been implemented,          system to address the management of
     particularly in high-income countries (78, 79).     polypharmacy (22). PESTEL and SWOT
     To illustrate the international initiatives,        exercises enable organizations to evaluate
     several polypharmacy guidance documents             issues that need to be addressed to ensure
     from different countries are listed in Annex 3.     that barriers to implementation are removed
                                                         and enablers are optimized (11). To support
     3.1 Implementing sustainable                        wider implementation of medication reviews
     programmes to address                               in selected populations, an economic analysis
     polypharmacy                                        tool has been developed to help countries
                                                         assess the potential economic benefits
     In the context of the third WHO Global Patient      of introducing and undertaking medication
     Safety Challenge: Medication Without Harm,          reviews in polypharmacy (80).
     countries are urged to take early priority action
     to protect patients from harm arising from          In addition to change management tools,
     polypharmacy by implementing programmes             some key factors that need to be considered
     which help to reduce inappropriate                  are described in the following. Existing health
     polypharmacy that are sustainable and can           care delivery models for polypharmacy should
     be delivered across the country. For the            be reassessed to ensure the pharmacist
     implementation of national, subnational             plays a key role within a multidisciplinary
     or local polypharmacy guidance and new              team alongside physicians and nurses (33).
     polypharmacy practices, it may be relevant          Medication reviews performed by health care
     to apply change management principles               professionals would need to be incorporated
     and theory-based implementation strategies.         in the design of clinical pathways in the
                                                         management of patients with multimorbidity
     Tools and theories to support the                   to facilitate workflow (81). Transfer of
     implementation process include Kotter’s             information across transitions of care is
     eight step process for leading change;              important to the management of appropriate
     political, economic, social, technological,         polypharmacy, because it ensures medications
     environmental and legal (PESTEL); and               that were reviewed and stopped are not
     strengths, weaknesses, opportunities and            restarted without proper justification.
     threats (SWOT) (11). A recent case study
     applied Kotter’s Eight step process for leading     Addressing organizational culture
     change and normalization process theory to          and multidisciplinary working
     assess successful polypharmacy management           The organizational dynamics within health
     activities in Europe, and provided advice           care systems can be complex and include

20    MEDICATION SAFETY IN POLYPHARMACY
the values, beliefs and assumptions held              OPtimising thERapy to prevent Avoidable
by those within an organization (33). Cultural        hospital admissions in the Multimorbid elderly
factors can facilitate or hinder the                  (OPERAM), aims to optimize existing
implementation of innovative practices in             pharmacological and non-pharmacological
managing polypharmacy. Failure to account             therapies to reduce avoidable hospital
for organizational culture is one of the main         admissions, particularly among older patients
reasons mentioned when evaluating why                 with multimorbidity in Europe. The goal of the
planned initiatives fail to overcome barriers (82).   study is to assess the impact of a structured
Not only should the culture of the health system      medication review with a software intervention,
as a whole be considered, but also the cultural       obtain and compare intervention studies
norms within given professions (83, 84). The          to find what is most effective and safe in order
results from a European Delphi study support          to determine the best and most cost–effective
that “prior to implementation of polypharmacy         measures for preventing avoidable hospital
management, the culture of an organization            admissions. Initiated in 2015, this study
should be assessed for both strengths                 is ongoing until year 2020 (87, 88).
and potential barriers to implementation” (11).
As with change management and systems                 Polypharmacy in chronic diseases: Reduction
thinking, there are multiple tools and                of Inappropriate Medication and Adverse drug
frameworks available to help decision-makers          events in older populations by electronic
identify the characteristics of the organizational    Decision Support (PRIMA-eDS), aims to provide
culture and to make appropriate modifications,        physicians with the best evidence regarding
in parallel with a safety culture assessment (85).    medication therapy for older patients with
                                                      multimorbidity through an electronic decision
Various studies have identified the necessity         support tool. The electronic decision support
and benefits of multidisciplinary collaboration       tool comprises of an indication check,
when addressing polypharmacy (10, 22).                recommendations based on guidelines,
Policy-makers would need to consider                  systematic reviews, drug interaction database,
addressing the legislative and contractual            renal dosing database, adverse effect
barriers that are in place if appropriate             database and the European list of inappropriate
polypharmacy is to be applied across                  medications for older people (89). The
the health care system. Political commitment          practicability and relevance of the tool
is required to ensure that dedicated resources        was evaluated through a randomized clinical
are allocated to the development of new               trial to test if discontinuing inappropriate
systems to address polypharmacy, but more             medications could improve patient outcomes,
importantly to strengthen the existing health         such as reduction of hospitalization or death;
care system. Political support is important           and the patient data entry was found to be too
to promote multidisciplinary team work (11).          time-consuming. Recent findings provide
For example, Medicines Optimisation Quality           more insight in the future development of
Framework of Northern Ireland recommends              the tool and the potential risk groups (90, 91).
medicines optimization (see Annex 1) activities
to be delivered by multidisciplinary teams (86).      Stimulating Innovation Management of
                                                      Polypharmacy and Adherence in The Elderly
3.2 Programmes on appropriate                         (SIMPATHY) project intends to stimulate,
polypharmacy                                          promote and support innovation across
                                                      the European Union in the management
To assist countries in understanding the              of appropriate polypharmacy and medication
hurdles and benefits of investing in                  adherence in older patients (78). This project
programmes addressing polypharmacy, this              aims to contribute to developing efficient and
report presents some programmes below.                sustainable health care systems. Through

                                                                  MEDICATION SAFETY IN POLYPHARMACY      21
stakeholder engagement, studies were
     undertaken in a range of different health care
     environments, including European Innovation
     Partnership on Active and Healthy Ageing
     reference sites. The studies provide a
     framework and politico-economic basis for
     a European Union-wide benchmarking survey
     of strategies being employed for polypharmacy
     and non-adherence management. Innovative
     multidisciplinary models were developed to
     support patients with long-term conditions
     using the professional expertise of pharmacists
     and physicians to reduce inappropriate
     polypharmacy and promote innovation in
     health care workforce development (11).
     A set of contextualized change management
     approaches and tools was developed to help
     politicians, regulators, health service providers,
     and other stakeholders to advance current
     practice by implementing organizational
     change, thereby improving the management
     of patients on polypharmacy (11, 80).

     In addition to creating a European knowledge-
     sharing network on polypharmacy and
     adherence management, the targeted
     dissemination of these validated findings may
     support policy development, implementation
     of strategic organizational development
     and the exchange of best practices (11).
     There is still room for improvement,
     as polypharmacy management is currently
     not widely addressed within most EU
     countries (22). This programme has generated
     information on which benchmarks can be
     applied for regional and national progress
     measurements, a definitive guidance on
     the role of key stakeholders and guidelines
     on how to initiate and manage the change
     process (11).

22    MEDICATION SAFETY IN POLYPHARMACY
Health systems
      approach to polypharmacy
                                                                                             4
Initiatives to address polypharmacy can be        prescribed. This can be harmful to patients,
complex and require strong leadership and         leads to ineffective therapies and waste of
management. Identifying a lead organization       resources, generating an unnecessary burden
and allocating responsibility could facilitate    for the patient as well as the whole society.
the implementation of polypharmacy                Inappropriate polypharmacy is a common
management initiatives at the regional or         example of irrational use of medicines.
national level. Organizational leadership         To address the challenge at the system level,
is vital in driving change to achieve effective   effective policies such as supportive incentive
polypharmacy management (11). The need            structures, education and management,
to address polypharmacy is universal, but         clear clinical guidance and appropriate
the challenge of leading change goes              training are considered far-reaching (93).
to the heart of the policies and culture of
organizations, requiring the active involvement   When deciding how to address polypharmacy,
of policy-makers, health care professionals       any solution needs to achieve the
and managers, as well as patients, families       aforementioned “quadruple aim”, so that
and caregivers (61). Often the window             quality of prescribing and outcomes from
of opportunity to ensure that change is           medication are improved whilst delivering
implemented is small, with three components       an economically sustainable solution that
being crucial: problem recognition, generation    will promote patient engagement across
of policy proposals, and a supportive political   the health care system without compromising
environment, to create a momentum for             the work life of health care professionals (35).
a change in public policy (92). Countries may     In many countries polypharmacy management
wish to consider using existing infrastructure    may not be widely addressed, which makes
such as pharmacovigilance centres                 it important to establish change management
(see Annex 1) and patient safety incident         strategies to support implementation
reporting and learning systems (RLS) to collect   at a national scale (22). An initial step would be
reports as well as to disseminate learning        to undertake a benchmarking survey so that
from harm occurring from polypharmacy             countries can assess their current status
and drug interactions (46, 49).                   with regard to polypharmacy. Business
                                                  operation tools such as PESTEL and SWOT
The irrational use of medicines is a global       analysis have been used for polypharmacy
issue. A WHO report, The World Medicines          programmes, and are helpful in identifying
Situation, estimated in 2004 that half of all     barriers and issues that countries would need
medicines are inappropriately prescribed,         to address in order to improve polypharmacy
dispensed or sold. Furthermore, half of all       management (11).
patients fail to take their medicine as

                                                               MEDICATION SAFETY IN POLYPHARMACY       23
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