Medication without harm Policy brief Medication without harm Policy brief Medication without harm: policy brief ISBN 978-92-4-006276-4 (electronic version) ISBN 978-92-4-006277-1 (print version) © World Health Organization 2023 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial- ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. 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The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by WHO in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use. Photo credits: The photos in pages 1, 4, 7, 11, 16, 17, 19, 20, 21 are from the WHO headquarters photo library © WHO Design and layout: Macro Graphics Pvt. Ltd., India Contents iii Contents Acknowledgements v Acronyms vi Executive summary vii Key messages viii 1. Introduction 1 1.1 Key concepts 2 1.2 Background 3 2. Errors during the medication use process 4 2.1 Prescribing 4 2.2 Transcribing 5 2.3 Dispensing 5 2.4 Administration 5 2.5 Monitoring 5 3. Scale of errors and contributory factors 6 3.1 Extremes of age 7 3.2 Multimorbidity 8 3.3 Polypharmacy 8 3.4 High-risk (high-alert) medicines 8 3.5 Antimicrobials and resistance 9 3.6 Palliative care 9 3.7 Transitions of care 9 3.8 Medicines as products 10 3.9 Health and care workers 11 3.10 Health care systems 12 4. Policy options to address medication errors 13 4.1 Safety culture and managing change 13 4.2 Reporting medication errors and learning 14 iv Medication without harm: policy brief 4.3 The three key action areas of the strategic framework 15 4.3.1 High-risk situations 15 4.3.2 Polypharmacy 16 4.3.3 Transitions of care 17 4.4 The four domains of the strategic framework 17 4.4.1 Patients and the public 17 4.4.2 Health and care workers 19 4.4.3 Medicines as products 20 4.4.4 Systems and practices of medication 20 5. Summary of the evidence, facts and findings 22 6. A pledge to sign 23 References 24 Annexes 32 Annex 1: Glossary 32 Annex 2: Pledge to support implementation of the third WHO Global Patient Safety Challenge: Medication Without Harm 36 Acknowledgements v Acknowledgements The development and publication of this document was coordinated by Neelam Dhingra-Kumar, Unit Head, Patient Safety Flagship: A Decade of Patient Safety 2021–2030, World Health Organization (WHO) headquarters, Geneva, Switzerland. An Internal Technical Working Group was constituted for development of technical products aligned with World Patient Safety Day, ‘Medication Without Harm’ involving nominated focal points from Medicines and Health Products/Pharmacovigilance (MHP/PVG), Antimicrobial Resistance (AMR), Health Workforce (HWF), Maternal, Newborn, Child, Adolescent Health and Ageing (MCA) and Traditional Complementary and Integrative Medicine (TCI) units. Principal writing and editorial team from Patient Safety Flagship (PSF), WHO headquarters: Priyadarshani Galappatthy, Alpana Mair, Neelam Dhingra-Kumar. Peer reviewers and other contributors from WHO headquarters: Sarah Elhassan Abuzeid (PSF), Onyema Ajuebor (HWF), Anand Balachandran (AMR), Nienke Bruinsma, (AMR), Matteo Cesari (MCA), Pradeep Kumar Dua (TCI), Lianne Marie Gonsalves (AMR), Nikhil Gupta (PSF), Minna Häkkinen-Wu (PSF), Maki Kajiwara (PSF), Catherine Kane (HWF), Aradhana Kohli (PSF), Kim Sungchol (TCI), Shanthi Narayan Pal (MCH/PVG), Irina Papieva (PSF), Ayda Taha (PSF), Fumihito Takanashi (MCH/PVG), Isabelle Wachsmuth (PSF). Contributors from WHO regional offices: Gertrude Avortri (Regional Office for Africa), Mafaten Chaouali (Regional Office for Europe), Jonas Gonseth-Garcia (Regional Office for the Americas), Hyppolite Kalambay Ntembwa (Regional Office for Africa), Pierre Claver Kariyo (Regional Office for Africa), Angeliki Katsap (Regional Office for Europe), Mondher Letaief (Regional Office for the Eastern Mediterranean), Nittita Prasopa-Plaizier (Regional Office for the Western Pacific), Joao Joaquim Rodrigues da Silva Breda (Regional Office for Europe), Aparna Singh Shah (Regional Office for South-East Asia), Tomas Zapata (Regional Office for Europe) and Evgeny Zheleznyakov (Regional Office for Africa). External peer reviewers: Graeme Kirkpatric, Head of Patient Safety (Advice & Guidance), NHS Improvement, Durham, United Kingdom of Great Britain and Ireland; Danini Marin, Ministry of Health Belize and Pan American Health Organisation; Nagwa Metwally, Patient for Patient safety Advocate, Egypt; Habu Mohamad Department of Medical Services, Ministry of Health, Kano State, Nigeria; Venus Mushinga, Ministry of Health and Childcare, Zimbabwe; Chinelo Ndefo Patients for Patient safety Network, Nigeria; Sudhir Prabhu, Father Muller Medical College, India; Dewani Ranaweera, Directorate Healthcare Quality and Safety, Ministry of Health, Sri Lanka; Caroline Samer, International Union for Basic and Clinical Pharmacology; Shazwani Shaharuddin, School of Pharmacy, Monash, Malaysia; Kailash Tamaria, All India Institute of Medical Science, New Delhi, India; Kazumi Tanaka, Department of Healthcare Quality and Safety, Gunma University, Japan. vi Medication without harm: policy brief Acronyms ADE adverse drug event ADR adverse drug reaction AMR antimicrobial Resistance LMICs low- and middle-income countries LASA look-alike sound-alike OECD Organization for Economic Co-operation and Development T&CM traditional and complementary medicines WHO World Health Organization Executive summary vii Executive summary Patient harm due to unsafe care is a leading cause of death and disability worldwide, and most of such harm is avoidable (1). Harm due to medicines and therapeutic options accounted for nearly 50% of the overall preventable harm in medical care (2). The pooled prevalence of preventable medication-related harm was 5% (1 in 20 patients) and one fourth of the harm was severe or potentially life-threatening (3). The prevalence of preventable medication-related harm was nearly double, 7% (1 on 25 patients) in low- and middle-income countries (LMICs) compared to 4% (1 in 14 patients) in high-income countries. This policy brief defines key concepts of medication safety and presents current evidence on the scale of the problem and the urgency of the situation. Medication errors occur throughout the medication use process; however, many recent studies indicate that most errors occur during prescribing and monitoring stages (3, 4). Evidence of medication-related harm in several contexts and environments are discussed. Policy options with benefits, advantages and opportunities to improve medication safety are suggested, including technological solutions. Establishment of medication safety committees within the organizational structure, appointing medication safety or patient safety officers and implementing national action plans on medication safety are recommended. Ensuring a culture of safety and managing changes to the culture in the workplace and in the health care system are important to improve medication safety. Reporting and learning systems for medication errors have been used in countries to identify errors, creating learning opportunities for preventing errors. Methods for addressing the priorities identified in the third WHO Global Patient Safety Challenge: Medication Without Harm are discussed using the strategic framework, focussing on the four domains and the three key action areas. Solutions that could be used in countries are proposed under the four domains of the strategic framework: the patient and the public, health and care workers, medicines as products, and systems and practices of medication and the three action areas: high-risk situations, polypharmacy and transitions of care. viii Medication without harm: policy brief Key messages Patient harm due to unsafe medical care is a leading cause of death and disability worldwide, and most patient harm is avoidable (1). One in 20 patients globally experience preventable medication related harm in medical care (3) Almost 50% of preventable patient harm is related to medicines and therapeutic interventions (2). A quarter of preventable harm is considered severe or life-threatening (3). Errors can occur at various stages of the medication use process: prescribing, transcribing, ordering, storage, dispensing, preparation, administration and monitoring. Globally most errors occur at the prescribing stage (53%) followed by the monitoring stage (36%), and in LMICs, almost 80% preventable errors occur at prescribing stage (3). The highest prevalence rates of preventable medication-related harm occur in elderly patient care units (17%) and among patients in highly specialized or surgical care (9%). Weak medication systems and/or human factors such as fatigue, burnout, poor environmental conditions or staff shortages contribute to medication errors. Many interventions to reduce the frequency and impact of medication errors are available, but their implementation varies. Patients in LMICs suffer greater harm than those in high- income countries. Countries are urged to develop targeted national action plans on medication safety and implement them to prevent medication errors and reduce avoidable medication- related harm. 01 02 03 04 Introduction 1 1 Introduction Everyone in the world will, at some point, take medicines to prevent or treat illness. Although medicines have increased life expectancy and patients live longer with a better quality of life despite disease, medicines can also cause severe harm (1). The trust that patients have in modern medicines and the health and care workers may also lead them to underestimate the risk of harm associated with medicines. Incidents related to medicines and other treatments account for the largest proportion of preventable patient harm (2). Severe harm due to medication errors affects not only the lives of patients and families but also the health and care workers, who are “second victims of harm”. Errors often occur in settings with weak health systems and practices and improving the culture of safety by various interventions can prevent medication errors. The report by the Institute of Medicine in the Unites States of America, To err is human in 1999 (5), shone a spotlight on preventable medical errors, and since its release, patient safety has become a priority in health care. Although harm during medical care poses a substantial burden on the world’s population, much of the evidence is from developed countries, whereas patients in Low-and Middle-Income Countries (LMICs) lose twice as many disability-adjusted life years due to medication- related harm than those in high-income countries (6). The highest prevalence rates of preventable medication-related harm were in the African (9%) and South-East Asian (9%) regions (3). Medication errors contribute 9% of the world’s total avoidable cost of health care, and 0.7% of total health expenditure worldwide, which amounts to US$ 42 billion estimated to be spent on medication errors (7). The Organisation for Economic Corporation and Development (OECD) report in 2022 indicated that 1 in 10 hospitalisations in OECD countries occur due to medication related harm and 1 in 5 hospitalised patients experience medication related harm. The OECD report estimated the annual cost of medication related harm in OECD countries alone to be over USD 54 million (8). This figure is equivalent to 11% of total pharmaceutical spending across 31 OECD countries. As the global population ages, more people will live with several rather than one disease, requiring many medicines (8). When providing access to health care for all, with universal health coverage, we must ensure that we do not harm patients due to the medicines they are given. Dispensing medicines, photo credit: WHO/Sergey Volkov 2 Medication without harm: policy brief This policy brief is aimed at creating awareness on the extent of global harm that occurs due to medication errors and explains the strategic framework proposed by WHO for member states, institutions, and facilities to address medication related harm. The framework was introduced with the launch of the third Global Patient Safety Challenge: Medication Without Harm by WHO in 2017 with the aim of reducing severe patient harm due to medication errors by 50% (9, 10). This document provides information to all stakeholders including, health and care workers, policymakers, healthcare facilities, institutions and patient care organizations on the extent of preventable medication related harm and the urgency to detect, address and prevent such harm. It also includes points for consideration by Member States, organizations, manufacturers and regulators to implement strategies to ensure medication safety, as applicable to them. To consolidate activities initiated on the Challenge, WHO selected ‘Medication Without Harm’ as the theme for the World Patient Safety Day 2022 (11). The Day provided an opportunity for health care leaders to drive change and work together with all stakeholders to make a difference in the lives of patients, families and to encourage health and care workers on the front line to implement the interventions proposed in the Challenge. This policy brief will help all stakeholders to identify policy level initiatives to ensure medication safety at all levels of heath care and in taking forward the activities initiated during the Global Patient Safety Challenge and the World Patient Safety Day 2022 on the theme “Medication Without Harm”. 1.1 Key concepts Adverse drug events, adverse drug reactions and medication errors Medicines may result in adverse drug events (ADEs), which are defined as “any injury resulting from medical interventions related to a drug” including both adverse drug reactions in which no error was involved as well as complications resulting from medication errors (12). Some ADEs are preventable and predictable, while other reactions to medicines are not predictable. The latter are known as adverse drug reactions (ADRs), defined as “a response to a drug which is noxious and unintended and that occurs at doses used in humans for prophylaxis, diagnosis or therapy of diseases or for the modification of physiological function” (13). Preventable ADEs are medication errors, defined as “any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient, or consumer. Such events may be related to professional practice, healthcare products, procedures, and systems, including prescribing, order communication, product labelling, packaging and nomenclature, compounding, dispensing, distribution, administration, education, monitoring, and use.” (14, 15). The relationship between adverse drug events, and medication errors are given in Figure 1 (16). Figure 1. Relations between medication errors and adverse drug events Adverse drug events Injury No injury Adverse drug reactions Not preventable Inherent risk of drugs Medication errors Preventable Ca us es O ut co m es Preventable adverse drug events Potential adverse drug events Trivial medication errors Source: Reproduced, with the permission of the publisher, from Otero and Schmitt (16). Introduction 3 1.2 Background The Seventy-second World Health Assembly (WHA) in 2019 adopted the resolution on Global action on patient safety considering that patient safety is a growing challenge to health service delivery globally (1). Subsequently, the Global Patient Safety Action Plan (GPSAP) 2021-2030 was endorsed by the Seventy- fourth WHA in 2021, aiming to provide WHO Member States and other stakeholders with an action- oriented framework to facilitate the implementation of strategic patient safety interventions across health systems, over the next 10 years, 2021–2030. The implementation of the third WHO Global Patient Safety Challenge: Medication Without Harm launched in 2017 is included under the Strategic Objective 1, Policies to eliminate avoidable harm in health care and Strategic Objective 3, Safety of clinical processes of the GPSAP. Specifically, the strategy 1.5 calls to Commit to prioritize and take action to achieve the goals of the Global Patient Safety Challenges with required leadership, coordination, expert advisory structures, and monitoring and evaluation, and the strategy 3.2 proposes the countries to Implement a programme to transform the safety of medication management and use, based on the third WHO Global Patient Safety Challenge: Medication Without Harm (1). The principle of the Challenge is that errors are not inevitable; the challenge is to reduce the prevalence of medication errors by addressing weaknesses in health care systems and practices. To achieve this, multilevel interventions are necessary at global, regional, national and facility levels and on the front line. The strategic framework proposed with three priority areas to focus and four domains under the Global Patient Safety Challenge: Medication Without Harm, are discussed in sections 4.3 and 4.4. Medicines are used in health care to cure and prevent diseases and to mitigate symptoms in all age groups. Medicines may be prescribed to patients by an appropriately qualified health professional or sometimes by informal health workers. They also may include products that have been purchased by patients or their carers for self-medication, such as Traditional and Complementary Medicine (T&CM) products for use with or in place of prescribed medicines. A systematic review reported an estimated average of about 58% people in Sub-Saharan Africa using T&CM products (17). Safety is a fundamental principle in the provision of T&CM medicines too, as adverse events may arise due to mistaken use of the wrong species of medicinal plants, wrong selection of raw or processed plant components and incorrect dosing. Use of medicines has increased because of increased adherence to disease-based guidance. The increase in use also results, however in increased hazards, errors and adverse events associated with medicines, which can be reduced or even prevented by improving the systems and practice of medication. 4 Medication without harm: policy brief 2 Errors during the medication use process The process of medication involves different healthcare professionals, mainly doctors, pharmacists and nurses, working in many settings. An error occurring at any stage that reaches a patient may result in harm and could involve everyone in the medication use process as well as the system in which they work. The definition or description of errors at each stage of the medication use process and the error rates that have been reported are summarized below. 2.1 Prescribing Prescribing errors defined as a mistake made by the prescriber when ordering a medication occur during prescription of a medicine, while writing a medication order or taking a therapeutic decision (15). It can also include failure to prescribe a drug necessary to treat a diagnosed disease or to prevent the adverse effects of other drugs. A recent systematic review found that the highest prevalence of preventable medication errors occurred during the prescribing stage of the medication use process, with an error rate of 53% (3). A systematic review of studies in hospitalized patients reported a median prescribing error rate of 7% in medication orders (18). The prescribing errors included errors in indication, drug–disease interactions, drug–drug interactions, dosing errors and inappropriate prescribing. The prescribing error rates reported in primary- care settings, care homes and secondary care in England were 4.2%, 8.3% and 9.0%, respectively (19), indicating that more prescribing errors occur in hospitals. Much higher prescribing error rates are reported from LMICs, with a pooled prevalence of 78 % from 30 studies from the WHO study (3) and error rates are up to 90% in some studies (20-22). Poor legibility seen in about 50% of prescriptions, incompleteness or errors in information about the patient and the medicines were contributory factors for errors in hand- written prescriptions in many LMICs (23, 24). Doctor prescribing medicines, photo credit: WHO/Fernando G. Revilla Errors during the medication use process 5 2.2 Transcribing Transcribing errors occur during order communication due to incorrect data recording by health and care workers (25). A study defined transcribing error in hospital practice as, any discrepancy between the physician’s medication order and the medication order written onto any document related to the patient concerned such as the medical record, medication chart, medication request sheet, discharge medication chart or any other similar document (26). The reported transcribing error rates varied from 15% to 70% (20). In another study, the rate of discrepancy between the medicines described by patients or caregivers and the medicines listed by their general practitioners or listed on the discharge letter or patient’s discharge medication list was 24% (27). 2.3 Dispensing Dispensing errors are defined as deviation from the prescriber’s order, made by staff in the pharmacy when distributing medicines to nursing units or to patients in an ambulatory pharmacy setting (15). A systematic review reported dispensing error rates between 0.015–33% (28). The most common factors associated with dispensing errors were high workload, low staffing, mix-up of “look-alike, sound-alike” (LASA) medicines, lack of knowledge or experience, distractions or interruptions, and communication problems within the dispensing team (29). 2.4 Administration Any discrepancy between how a medicine is given to a patient and the directions for administration from the physician or hospital guidelines is regarded as an administration error (15). The WHO systematic review reported that overall prevalence of administration errors was 22% (3) while the median rate of administration errors excluding errors in administration time was 10.5% (30). 2.5 Monitoring Failure to review a prescribed regimen for appropriateness and to detect problems or failure to use appropriate clinical or laboratory data for assessment of the patient’s response according to prescription theory is termed a monitoring error (15). Monitoring errors were the next most common preventable medication errors after prescribing errors, with error rates of 36% and 47% reported in systematic reviews (3, 4). Picking up medicines for the child at the pharmacy, photo credit: WHO/Harold Ruiz 6 Medication without harm: policy brief 3 Scale of errors and contributory factors Unsafe care is one of the leading causes of morbidity and mortality in the world. It occurs at all levels of health care in countries, regardless of their income status. An average of one in 10 patients in high-income countries is subjected to an adverse event during hospitalization (31). Estimates for LMICs suggest up to one in four patients is harmed, with 134 million adverse events occurring in hospitals annually, contributing to about 2.6 million deaths (1, 32). In a meta-analysis of 70 studies involving 337 025 patients, incidents related to drugs (25%) and other treatments (24%) accounted for the largest proportions of preventable patient harm (2). In primary and ambulatory care in the OECD countries, as many as 4 of 10 patients are harmed due to errors in care, and up to 80% of the harm could be avoided (33). In an OECD report, it was estimated that 15% of hospital expenditure and activity in those countries can be attributed to treating safety failures, medication error being a common cause (34). Medication errors and error-related ADEs occur in all health care settings which are responsible for considerable harm to patients (35). The recent systematic review of 100 studies on preventable medication harm indicated that one in 20 patients is exposed to medication errors, of which 26% are considered severe or life-threatening (3). In the study, the prevalence of preventable medication related harm in LMIC was 6.9% (1 in 15 patients) while in HICs prevalence was 4% (1 in 25 patients). The highest prevalence rates for preventable medication-related harm was found in elderly patient care units (17%), highly specialized or surgical care (9%), intensive care units (7%) and emergency departments (6%) (3). In England, it was estimated that 237 million medication errors occur each year, causing 712 deaths and contributing to another 1708 deaths during initial hospitalization (36). Preventable ADRs were estimated to cost the National Health Service £98.5 million per annum (36). Most of the available studies have been conducted in hospitals, although there is an international move to manage care in primary care, ambulatory settings or patients’ homes. The pooled prevalence of ADRs in primary care has been shown to be 8.32% in a recent systematic review (37) and in English general practice, most were prescribing/ monitoring errors (38). Although data on patient harm are reported less often from LMICs than high-income countries, the available data indicate a higher prevalence of preventable patient harm in LMICs. A retrospective case record review involving 8 developing countries reported at least 1 adverse event in 8.2% of 15, 548 records reviewed with a range of 2.5-18.4% per country (39). Of the adverse events, 83% were judged to be preventable and about 30% were associated with deaths of the patient; 34% of the adverse events were therapeutic errors in relatively non-complex clinical situations (39). The available evidence of risks to patient safety associated with medication globally calls for new strategies to manage the risks. Studies on medication errors have identified contributory factors related to patients, health and care workers and medications. They include the number of medicines used by a patient, the number of comorbid conditions, the use of high-risk (high-alert) medicines and involvement of several health and Scale of errors and contributory factors 7 care workers in care. A study on hospital admissions for drug-related events identified older age, starting new high-risk medicines and receiving more than 5 medicines as the risk factors (40). A systematic review reported prescription of certain medicines or classes of medicines, polypharmacy, older age, female gender, poor renal or hepatic function, having many comorbid conditions, length of hospital stay, history of drug allergy or sensitivity and the compliance of the patient as risk factors necessitating pharmaceutical interventions (41). Some of these factors are discussed in detail below. 3.1 Extremes of age Medication errors are most likely to occur in very young and older persons, who are less likely to tolerate ADRs and have more severe outcomes. Recent systematic review on preventable medication-related harm reported highest prevalence rates of 17% in elderly patient care units (3). A systematic review of the incidence and nature of medication errors in children showed a wide variation in incidence and identified it as a concern for paediatric population (42). In very young children, the body systems such as the liver and kidney that are responsible for eliminating medicines from the body may not be fully developed, increasing the likelihood of harm. Calculation of drug doses according to the weight of children is one reason for errors. Older persons react differently from younger people to medicines, because of changes in organ function, the muscle: body-fat ratio and the rate of clearance of medicines. They are therefore at increased risk of medication-related harm (43). Age-related physiological impairment and comorbid conditions require the use of several medicines, increasing susceptibility to adverse effects, drug–drug interactions and drug–condition interactions (44). In older people, 25–40% of hospital admissions were found to be linked to medication errors (40). Furthermore, older people often take psychotropic medicines, increasing the Older patient with the daily medicines, photo credit: WHO/Quinn Mattingly 8 Medication without harm: policy brief likelihood of falls (45). In residential care facilities, the rate of falls is much higher than elsewhere, and they progress to more serious complications (46). Use of opioids, antiepileptics and polypharmacy was significantly associated with an increased risk of falling (47). Reduced cognitive function in older persons increases the risk of wandering and acquiring injuries due to falls (48). Patients with dementia tend to have more comorbid conditions and are more likely to have prescriptions for more medicines, which increases their risk of polypharmacy-related safety issues (49). 3.2 Multimorbidity Multimorbidity is defined as the presence of two or more long-term health conditions (50, 51). Epidemiological data indicate that multimorbidity increases markedly with age and is present in almost two thirds of individuals aged over 80 years (50). In a general practice, 27% of patients had multimorbidity (51). On average, people with multimorbidity have at least three long-term conditions, cardiovascular (88%), metabolic (62%) and rheumatic conditions (40%) being the commonest. A meta-analysis of studies of primary care showed that multimorbidity involving physical and mental conditions was associated with an increased risk for “active patient safety incidents”, including prescribing errors (52). Multimorbidity poses an increased economic burden due to greater use of health services, including community-based health services and hospitalization (three times higher), in some cases due to harm from medicines (53-55). Frailty should be considered independently of age and multimorbidity. In a systematic review, frail patients were found to be more likely to receive several and to be at increased risk of harm (56). These patients have higher risks of hospitalization, disability and mortality (57, 58). 3.3 Polypharmacy Concurrent use of several medicines is referred to as polypharmacy. Although there is no standard definition, polypharmacy is usually defined as concurrent use of five or more medicines that include over-the-counter, prescription and/or T&CM products (59, 60). More medicines might, however, be required and appropriate for some patients. Certain criteria can be used to determine the appropriateness of polypharmacy (59). Polypharmacy is a growing problem with increased longevity and multimorbidity. Complex treatment regimens also present a risk of non-adherence. These factors increase the likelihood of morbidity, unplanned admissions, readmissions and prolonged hospital stays. Despite extensive advances in pharmacotherapy, few clinical guidelines are available for adults with multiple morbidities. Prescribing is largely based on evidence-based guidance for single diseases, which does not generally consider multimorbidity (61, 62). Consequently, patients are often prescribed several medicines recommended by different specialists according to disease-specific guidelines, which, in combination, make management of multimorbidity difficult and may lead to patient harm (63). 3.4 High-risk (high-alert) medicines Many medicines pose a higher risk of harm when used in error or inappropriately. These are referred to as “high-risk (high-alert) medicines” (64, 65), and the specific medicines identified may differ from country to country. A systematic review reported error rates ranging from 0·24 to 89·6 per 100 medication orders that occur due to high-alert medicines (66). Use of these medicines by vulnerable groups such as children and the elderly may increase the risk of harm. In hospitals, the medicines commonly implicated as high-risk are anti-infective agents, potassium and other electrolytes, opioids and other sedatives, chemotherapeutic agents, heparin and anticoagulants (64). Medicines commonly implicated in primary care include Scale of errors and contributory factors 9 antiplatelets, diuretics, anticoagulants and non-steroidal anti-inflammatory drugs. The Institute for Safe Medicine Practices has identified high-alert medicines lists used in acute care settings (65), community and ambulatory care settings (67), and these lists can be used as guides by countries or institutions that do not have their own lists of high-risk medicines. 3.5 Antimicrobials and resistance Inappropriate and increasing use of antimicrobials has led to the development of resistance, which is a global concern. Antimicrobial resistance (AMR) has made many infections, particularly bacterial infections, increasingly difficult or even impossible to treat. Without effective medicines, the number of people with severe microbial infections will increase, resulting in an increase in the number of people who die from these infections (68). In 2019, 4.95 million deaths were associated with AMR, with the highest death rates attributable to AMR occurring in western sub-Saharan Africa at an estimated 27.3 deaths per 100,000 (69). The six leading pathogens for deaths associated with resistance in 2019 were Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, responsible for nearly 1 million deaths (69). The rate of resistance to the commonly used antibiotic ciprofloxacin, varied from 8.4% to 92.9% for Escherichia coli and from 4.1% to 79.4% for Klebsiella pneumoniae in countries reporting to the WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) (70). Antimicrobials could also cause allergic reactions, including anaphylaxis and death, other adverse effects in various systems and Clostridium difficile infections after prolonged use (71). 3.6 Palliative care Most medical errors in palliative care are related to medicines used for symptom control, particularly opioid analgesics (72). Erroneous selection of medicines or of their dosage or administration can result in either undertreatment of distressing symptoms or intoxication, both causing unnecessary suffering for the patient. Opioids are high-risk medicines, and 84% of errors in one study were due to opioids (73). Most errors involved morphine (35%) or hydro morphine (29%). Patients were more likely to receive a lower dose of an opioid than ordered, as a direct result of an error (57%) and such errors adversely impact pain and/or symptom management in 42% of patients. A systematic review, however, showed paucity of information on the incidence, types and patient impact of opioid errors in adult oncology and palliative care (74). Defining, identifying and quantifying error reporting practices for these populations should be a component of medication safety initiatives in palliative care. 3.7 Transitions of care Unintended discrepancies in medication can arise when patients transit through care settings. Transitions of care are the physical locations or contacts with a health care professional to which a patient moves or returns to receive health care (75). A Cochrane review found that 56% of people are at risk of having one or more medication-related discrepancies, and 11–59% are potentially at risk of harm during care transitions (76). Discrepancies in medication orders are common, and they increase with the number of medicines prescribed. At transitions of care, polypharmacy and an insufficient knowledge of the patients’ medication history are important causes of prescribing errors (77). Another systematic review reported a median rate of medication error or unintentional medication discrepancy of nearly 50% in adult and elderly patients after hospital discharge (78). About 20% of adult and elderly patients were affected by ADEs after hospital discharge. Although most of the studies were conducted in high-income countries, such discrepancies have also been observed in LMICs (79-81). 10 Medication without harm: policy brief 3.8 Medicines as products Substandard and falsified medicines The safety and quality of medicines in different countries varies. One of the main causes of medication- related harm globally is substandard and falsified medicines (82-84). Patient harm occurs when patients do not receive the expected benefits, due to substandard medicines and when they are exposed to harmful chemicals used to adulterate medical products. The global prevalence of poor-quality medicines in a study in 2018 was 13.6%, with a regional prevalence of 18.7% in Africa and 13.7% in Asia (82). In the same study, 19.1% of antimalarials and 12.4% of antibiotics were substandard or falsified. The global total value of falsified medicinal products was US$ 4.4 billion in 2016 (83). An estimated 1 in 10 medical products in LMICs is substandard or falsified (84), and LMICs spend an estimated US$ 30.5 billion on such medicines, representing 10.5% of medicines sampled in the supply chain in these countries (85). Products subjected to fraudulent activities, apart from antimicrobials, include medicines for pain management, diabetes and cancer. Substandard and falsified antimicrobials contribute to antimicrobial resistance. “Look-alike and sound-alike” medicines The names, packaging or labelling of medicines can be confusing, and clear information is sometimes lacking. Confusing “look-alike and sound-alike” (LASA) names, labelling and packaging are frequent sources of error and medication-related harm, with 6–14% of all errors due to LASA products (86, 87). LASA pairs identified are published by the Institute for Safe Medication Practices, and “tall man lettering” with capitalisation of confused letters can be used to identify these medicines accurately (88). Figure 2b. Examples of some injectable products of LASA medicines Source : Reproduced from World Health Organisation publication (86). Figure 2a. Examples of tablets of LASA medicines Source : Reproduced from World Health Organisation publication (86). Scale of errors and contributory factors 11 Medicines more likely to cause harm Some medicines are more closely associated with harm than others. The medicines associated with more preventable ADEs include anticoagulants or antiplatelets, cardiovascular medicines, diuretics, hypoglycaemics analgesics, antibiotics and antiepileptic medicines, (37, 78). The metanalysis of studies on preventable medication harm has identified that medicines for nervous system conditions (21%) cardiovascular diseases (16%), anti-inflammatory and antirheumatic drugs (15%), antimicrobials (12%) and anti-thrombotics (11%) were the medicines or medicine classes most commonly responsible for harm (3). Certain genetic factors can predispose to adverse drug reactions (89) and in the presence of known genetic factors, prescribing certain medicines can also result in a medication error. Traditional and complementary medicines There are regulatory and cultural differences in the preparation and use of allopathic and T&CM products. A critical component is quality control of T&CM products, important from the perspective of patient safety. Incorrect, and inappropriate usage of T&CM, even though of natural origin can lead to unwanted effects. Moreover, some medicinal plants are inherently toxic. Similarity in the colour, consistency, aroma and the taste of the pieces of raw herbs, powders or liquid herbal preparations and colour, shape, size of the tablets and capsules can contribute to errors with T&CM products too (87). Several medicinal plants are known by dissimilar common names in different languages in different parts of the world, which could lead to wrong identification. Adverse events may also arise from the mistaken use of the wrong species of medicinal plants, incorrect dosing, or errors in the use of herbal medicines both by health-care providers and consumers. 3.9 Health and care workers Use of medicines involves collaboration among several health and care workers throughout the process. Physical factors such as fatigue, burnout, distraction and interruption, poor information transfer and psychological factors related to inexperience, workload and insufficient decision support were given as reasons for errors by health care staff (90, 91). Physician burnout doubled the patient safety incident rate and burnout was greatest in physicians still in training or residency, in those who worked in hospitals, specifically in emergency medicines or working in LMIC settings (91). Evidence also shows that unacceptable behaviour of health and care workers negatively affects their clinical performance, quality of care, workplace productivity and patient outcomes (92). Doctors, pharmacists and nurses are the main health care providers involved in the medication process. They may experience a variety of emotions after a medication error, including guilt, shame, anxiety, fear and depression (93). Health care providers involved in adverse events who subsequently have difficulty in coping with their emotions are thus considered “second victims” of patient safety incidents who need to be supported (94). Physician training the medical staff, photo credit: WHO/Winnie Romeril 12 Medication without harm: policy brief Informal health care providers, who function as health workers in LMICs (95), often provide medicines to patients, which may be a risk factor for medication safety and patient harm due to lack of knowledge, expertise, and poor adherence to national clinical guidelines. Delegation of medication related responsibilities is more acceptable within a framework that adequately supports them in the process, backed by appropriate policy, skills, training, and supervisory arrangements (96). 3.10 Health care systems The health care environment is an important determinant of the risk of medication errors. The systems and environment in high-income countries, with electronic prescribing, bar-coded dispensing, automated devices for administration and established error reporting and learning systems, is more likely to prevent medication errors (29). Health care systems in most LMICs involve handwritten prescriptions, manual dispensing of medicines to large number of patients with no clinical pharmacy services to back up prescribers (20-24). In addition, there is under-reporting of errors due to factors such as health care providers’ workload, lack of reporting systems, education, training, institutional policies and protocols, and the fear of disciplinary action. The system factors that contribute to medication errors may differ in different settings such as perioperative care (97). Lack of medication reconciliation, weak drug distribution systems, poor-quality prescriptions, deviation from procedures, including distractions during administration and excessive workloads are other system factors that contribute to errors (98). Policy options to address medication errors 13 Policy options to address medication errors 4 Clear policies, organizational leadership, data for improving safety, skilled health and care workers and effective involvement of patients in their care are all necessary to ensure sustainable, significant improvements in the safety of health care (99). WHO initiated its third Global Patient Safety Challenge: Medication Without Harm to address several issues related to medication safety, including strengthening systems to reduce errors and avoidable harm on the principle that many errors are not inevitable but are provoked by weak health care systems. The Challenge also seeks to reduce the frequency of medication errors and their impact by tackling some of the inherent system weaknesses. Countries are encouraged to identify their own priorities and the actions necessary to address the issues using this framework. Each country needs to assess its current status on medication safety, based on local evidence and address the four domains and three priority areas outlined in the strategic framework. It is proposed that countries prioritize action on medication safety, designate leaders to drive action and devise their own programmes based on local priorities. The policy options to address medication safety, according to benefits, advantages and opportunities, include use of technology-based solutions where available, formation of medication safety committees in their organizational structure, appointing medication safety or patient safety officers, and implementing national action plans on medication safety. Some of the key policy options to consider are described in detail below. 4.1 Safety culture and managing change A culture of safety in the workplace or health care system is necessary to ensure medication safety. A systems approach is taken in patient safety, as many factors must be addressed to reduce harm (100). A systems approach includes the conditions in which individuals work and attempts to build defences to avert errors or mitigate their effects. The “Swiss cheese” model as applied to medication safety illustrates potential defences throughout medicines use (Fig. 2). A culture of safety has five attributes to be operationalized by health workers through safety management systems (15): All workers accept responsibility for the safety of themselves, their co-workers, patients and visitors. Workers prioritize safety over financial and operational goals. The system encourages and rewards the identification, communication and resolution of safety issues. The system provides for organizational learning from accidents. The system provides appropriate resources, structure and accountability to maintain effective safety systems. 14 Medication without harm: policy brief Teamwork and communication training interventions improved the safety culture in emergency department settings and may positively affect patient outcome (101). Organizations with an effective culture of safety are committed to safety as a high priority throughout the organization. Failure to account for organizational safety culture is one of the main reasons that planned change initiatives are unable to overcome barriers. Not only the culture of the health system but also the cultural norms in different professions require due consideration. Figure 3. “Swiss cheese” model as applied to medication safety Potential defences Communication and collaboration between health care professionals Patient received the wrong medication Error went unnoticed even after patient deteriorated clinically and had to be admitted to hospital Patient continued to receive wrong medication even while in hospital Access to health records to enable review Medication review Patient engagement and education Medication reconciliation (Identied by pharmacist) A. B. C. D. E. Gaps in defences Discrepancy in discharge medication, olanzapine prescribed instead of lansoprazole Source: Adapted with the permission of the publisher, from Reason J (100) and reproduced from World Health Organization, Technical report (75). 4.2 Reporting medication errors and learning The role of a patient safety reporting and learning system is to improve patient safety by learning from failures (102). The national reporting systems in countries identify the common errors reported especially those that have caused serious patient harm and learn from those to take preventive actions (103). Although each event is unique, likely similarities and patterns in sources of risk can be used to prevent similar incidents. European Union legislation passed in 2015 requires information on medication errors to be collected and reported through national pharmacovigilance systems for evaluation and assessment (104). A clear distinction is made between adverse drug reactions which are not preventable, medication errors, resulting in preventable adverse events, medication errors that do not cause harm, intercepted medication errors and potential errors. National authorities responsible for pharmacovigilance are requested to collaborate and exchange information on medication errors resulting in patient harm with national patient safety organizations. The reporting systems should also allow reporting by patients and include reporting of errors or adverse events related to T&CM products to identify errors and to implement preventive strategies related to T&CM products. LMICs face many challenges regarding pharmacovigilance and medication error reporting (105). They have limited integration of pharmacovigilance systems, reporting tools need to be translated into local languages, there are few well-trained pharmacovigilance personnel, and they have little budgetary support from their national governments. Health and care workers are less aware of error reporting, and a Policy options to address medication errors 15 culture of blame contributes to very low reporting rates and poor-quality spontaneous reports, which limit learning from reports. Countries need to address these factors to establish effective error-reporting and learning systems. 4.3 The three key action areas of the strategic framework The WHO Global Patient Safety Challenge: Medication Without Harm introduced a strategic framework with three key action areas: high-risk situations, polypharmacy and transitions of care and highlights four domains in which medication safety may be compromised: patients and the public, health and care workers, medicines as products, and systems and practices of medicines use. (see figure 3) Figure 4. Four domains, 16 subdomains and three action areas of the strategic framework
4.3.1 High-risk situations The WHO technical report Medication safety in high-risk situations (64) elaborates four broad factors that influence medication safety in high-risk situations: medication, provider, patient and systems factors. Because of the complexity of health systems, a single strategy is rarely sufficient for addressing the risks associated with each high-risk medication. The following measures may be considered (64): 16 Medication without harm: policy brief Draw up a list of high-risk medicines: A list for each country or setting is preferred to focus action on errors that occur locally. Combine many error reduction strategies: Choose risk reduction strategies that affect as many steps of the medication management system as possible. Examples include having forcing functions (see Glossary), in computerised systems (e.g., need to enter patient’s essential details including laboratory results before allowing to prescribe some high-alert medicines or a dose) and other strategies such as staff education and passive information dissemination on high-risk situations. Name, package and label LASA medicines and high- alert medicines: label according to recommendations such as with “tall man” lettering and using high alert labels (86, 87). Use strategies that have been implemented successfully: these are often proven effective, are recommended by experts and are sustainable (106, 107). Use standardized medication charts with limited use of abbreviations and symbols: after introduction of the national inpatient medication chart in Australia, the number of prescribing errors per patient decreased by almost one third (108). 4.3.2 Polypharmacy As polypharmacy is identified as an important contributory factor for medication errors, programmes to reduce inappropriate polypharmacy that are sustainable and can be delivered throughout the healthcare systems are recommended (59). Actions to be considered include the following: Review of medicines at initiation and at care transitions: a seven-step method for conducting a medication review is proposed (59). Pharmacist- led medication reviews and reconciliation reduced the number of hospital admissions (109). Medication reviews can reduce ADEs in older people living in the community and in residential aged care facilities (110, 111). Patients in a hospital, photo credit: WHO/Emmanuel Eraly Pharmacist dispensing medicines, photo credit: WHO/Eduardo Martino Policy options to address medication errors 17 De-prescribing: consist of tapering off, stopping, discontinuing or withdrawing medicines. Deprescribing, minimizes the dosage, the number of tablets and the frequency of administration (112). STOPP/START criteria have been used in de-prescribing and ensuring the use of indicated medicines (113). Adding an indication to a prescription: shown to be useful for detecting inappropriate polypharmacy (114). Prioritizing patients for medication review: they include residents of care homes, patients on high-alert medicines, patients taking 10 or more medicines, patients with two or more comorbid conditions, frail patients, those with dementia and patients in palliative care (115). 4.3.3 Transitions of care Many medication discrepancies are noted to occur during care transitions (75). Solutions to ensure medication safety at transitions of care include involving people, technology, systems and processes. Some interventions known to reduce errors are listed below: Medication reconciliation programmes: medication reconciliation facilitates transfer of accurate, complete information on a patient’s medication at interfaces of care (76). Involvement of pharmacists in medicines reconciliation is effective, economically viable and reduces discrepancies after discharge (116). Multicomponent interventions based on education of staff and guidelines: shown to be effective at achieving almost four times more de-prescribing of inappropriate medications by the time of discharge of patient from the hospital (117). Information technology intervention: computerized clinical records applied with feedback, educational outreach and dedicated support was effective in reducing various medication errors (118). The three WHO technical reports on medication safety in high-risk situations (64), polypharmacy (59) and transitions of care (75) elaborate on the strategies to prevent medication errors in these key areas. 4.4 The four domains of the strategic framework The strategic framework proposed in the WHO Global Patient Safety Challenge: Medication Without Harm identifies four domains and 16 subdomains to address medication safety (Fig. 3). The interventions that can be taken under each of the domains are discussed below. 4.4.1 Patients and the public In modern health care systems, the patient’s role has evolved from being a passive recipient of medical care to active, empowered, informed “producers” of health (119). Involving patients in the design and delivery of a programme helps to ensure effective implementation and sustainability of measures to address medication safety. Countries and institutions can involve patients on the following subdomains: Public awareness and medication literacy: make use of the WHO materials such as “KNOW. CHECK. ASK” campaign (120) to improve medication literacy. Among consumers, there is a widespread misconception that T&CM products are ‘natural’ and hence ‘safe’ and carry no risk. However, incorrect, and inappropriate usage of T&CM products can also lead to unwanted effects and public should be made aware of this. 18 Medication without harm: policy brief Patient engagement: engage patients and providers to improve service delivery and governance (124). The WHO patient engagement tool, “5 Moments for Medication Safety” on questions patients should ask on starting, taking, adding, reviewing and stopping a medication can be used (121). There are other patient engagement tools for medication safety, available in countries and organizations (122-123). Patient- held medication lists or records, sometimes called “medication passports” (paper or electronic), can help to optimize patients’ medicines (125). These tools are received positively by patients (126). Updated medication lists, can also be helpful at care transitions (127). Reporting by patients: empower patients and pharmacovigilance systems by allowing patients to report any concerns about their medications (102). Involvement of patient organizations: engage with patients’ organizations to provide patients’ perspectives on improving medication safety . Fig. 5. The 5 moments of medication safety Starting a medication Adding a medication Stopping my medication Taking my medication Reviewing my medications What is the name of this medication and what is it for? What are the risks and possible side-effects? Is there another way of treating my condition? Have I tod my health professional about my allergies and other health conditions? How should I store this medication? When should I take this medication and how much should I take each time? How should I take the medication? Is there anything related to food and drink that I should know while taking this medication? What should I do if I miss a dose of this medication? What should I do if I have side-effects? Do I really need any other medication? Have I told my health professional about the medications I am already taking? Can this medication interact with my other medications? What should I do if I suspect an interaction? Will I be able to manage multiple medications correctly? Do I keep a list of all my medications? How long should I take each medication? Am I taking any medications I no longer need? Does a health professional check my medications regularly? How often should my medications be reviewed? When should I stop each medication? Should any of my medications not be stopped suddenly? What should I do if I run out of medication? If I have to stop my medication due to an unwanted effect, where shold I report this? What should I do with leftover or expired mediations? Source: World Health Organization Policy options to address medication errors 19 4.4.2 Health and care workers Health and care workers have a key role to play in ensuring medication safety. Health care leaders should raise awareness about medication safety and prioritize areas to be addressed based on an assessment of a country or institution. The subdomains to be addressed are as follows: Education and training: use the WHO Curriculum Guide on Patient Safety (128), section on medication safety, to develop and update the skills of all categories of health and care workers in safe medication practices, and to mentor new team members on safe medication systems and practice. Training of specialists in the field of clinical pharmacology will enable training of health and care workers on activities pertaining to medication safety (129). Communication and teamwork: provide clear and full information on medicines to all members of the clinical team throughout the process of care to prevent medication errors. Read back during verbal orders to ensure that the correct order is communicated to prevent errors. Capability at points of care: prescribe rationally and transcribe, dispense, administer and monitor medicines carefully using methods such as technology, legible writing, avoiding error prone abbreviations and checking on 5 rights (right patient, drug, dose, route and time). Health and care workers need to be aware of situations in which the risk of medication error is higher and ensure that safety measures are followed. Incident reporting and learning: report all medication errors noted and share lessons learnt following any error with the healthcare team and with patients, when possible, to prevent such errors. Medicine being dispensed at a pharmacy, photo credit: WHO/Atul Loke 20 Medication without harm: policy brief 4.4.3 Medicines as products Attention to some aspects of medicines as products can minimize errors at all stages of their use, particularly on the following subdomains: Product quality and safety: implement robust regulatory systems and processes to ensure that procured medicines are safe. The WHO prequalification programme for pharmaceuticals can help LMICs to obtain quality-assured pharmaceuticals (130, 131). A well-functioning regulatory system and robust regulatory processes are necessary to address the issue of substandard and falsified medicines. Education and awareness-raising are first steps in preventing the use of substandard and falsified medicines (132). Quality control of T&CM products also need to be ensured for safety. Naming, labelling and packaging: consider clarity in labelling, packaging and availability of patient information during registration of pharmaceuticals. Label high-alert medicines and LASA medicines for clear identification using ‘tall man’ lettering and auxiliary labelling. Indicate the names of medicinal plants included in T&CM products for correct identification. Logistics, storage and disposal: store the medicines according to the manufacturer’s instructions and maintain the cold chain specific to each product. Store high-alert and LASA medicines separately to prevent errors. Dispose medicines according to the guidelines. The right products at points of care: make available appropriate medicinal products at the point of care for patients and select medicines rationally according to clinical guidelines. Develop and have an updated Essential Medicines List for the country and the WHO model lists of essential medicines can be used for this purpose (133). Prescribe appropriately in the context of multi-morbidity and ageing. Empower patients so that patients can participate in decision-making to receive the medicines they would be happy to use (134). 4.4.4 Systems and practices of medication A systems approach is recommended to address errors that might arise due to unsafe working conditions, with strategies for the entire health care system, especially on the following subdomains: Leadership and governance: review health care systems in countries to identify areas for improving medication safety; design and implement medication safety action plans with stakeholders, involve patients and the public; and establish medication safety committees and appoint medication safety or patient safety officers. Prescribing, preparation and dispensing: use electronic prescribing and automated dispending where feasible. Electronic prescribing reduces the risk of medication errors due to poor legibility and ADEs (135, 136), although this may not be possible in some clinical and geographical settings such as LMICs. Bar-coding improves patient safety in hospitals at a relatively low cost per avoided Medicines in a pharmacy, photo credit: WHO/Yoshi Shimizu Policy options to address medication errors 21 error (137–139). Train staff on use of technology such as automated dispensing, to reduce dispensing error rates (27). Medication reconciliation and review, pharmacist involvement in medication safety, are effective in reducing medication errors in acute care (140). Administration and patient monitoring: implement strategies specific for each setting and category, prioritizing high alert medicines, perioperative care, emergency departments, care of children and the elderly to prevent administration and monitoring errors (141, 142). Medication error analysis, computerized provider-order entry systems, employing emergency clinical pharmacists, independent double checking and proactive monitoring are also useful (141). Monitoring and evaluation: adopt change management strategies to ensure monitoring and evaluation of progress in medication safety programmes. Implement medication error monitoring systems to determine the impact of interventions (143). A patient is taking medicines, photo credit: WHO/Sergey Volkov 22 Medication without harm: policy brief Summary of the evidence, facts and findings 5 Unsafe medication practices and medication errors are a leading cause of injury and avoidable harm in health care systems throughout the world. Severe harm due to medication errors not only affect the lives of patients and their families but also those of health and care workers. Medication-related harm accounted for nearly half of all preventable harm in medical care. About one in 20 patients experience preventable medication related harm in medical care, and about a quarter of this harm is considered severe or life-threatening. Globally, if medication errors are prevented, 0.7% of global health expenditure or a loss of $42 billion USD can be avoided every year. Patients in LMICs lose twice as many disability- adjusted life years due to medication-related harm as those in high-income countries. The highest prevalence rate of preventable medication harm is seen in elderly care units, often in patients with high rates of comorbid conditions and thus on polypharmacy. The prevalence is also high in acute specialized care settings, such as intensive care units, and associated with surgery. Medication errors occur throughout the medication use process and the prescribing and monitoring stages of medication use were the main sources of preventable harm. Medication errors occur in the context of weak medication systems and/or human factors such as fatigue, poor environmental conditions or staff shortages, which may result in severe harm, disability and even death. Many interventions have been developed to address the frequency and impact of medication errors, but their implementation varies. Adoption of electronic health records and electronic prescribing has helped avert preventable harm at the prescribing and transcribing stages, and pharmacist-led medication reconciliation has helped to reduce errors at transitions of care. Wide mobilization of stakeholders for sustained action is required to prevent medication errors. WHO launched the third Global Patient Safety Challenge: Medication Without Harm to address patient harm due to medicines, which proposes a strategic framework and key interventions. Priorities for action are high-risk situations, polypharmacy and transitions of care. Four domains have been identified for targeted action: patients and the public, health and care workers, medicines as products, and systems and practices of medication. WHO selected ‘Medication Without Harm’ as the theme of World Patient Safety Day 2022 to consolidate the work on the Challenge and to strengthen and implement the proposed actions. The goal is to achieve widespread engagement and commitment of WHO Member States and professional bodies for action to reduce the harm associated with medicines. This policy brief identifies the key problem areas and proposes several solutions within the strategic framework to improve medication safety globally. Countries could consider the options outlined above to reduce avoidable harm due to medicines. Prioritization of the three key action areas and implementation of interventions in each of the four domains of the strategic framework, that are relevant for the country or institution, would contribute significantly in reducing medication-related harm. Countries need to also consider how they will monitor and evaluate progress effectively. The box below is a pledge that countries are requested sign listing the elements that could be considered to address medication safety. A pledge to sign 23 A pledge to sign 6 Countries are asked to sign a pledge (Annex 2) to support the Challenge and to encourage as many of their health care facilities as possible to also pledge adoption of the Challenge. A five-point plan has been developed to facilitate adoption: 1. Designate a national coordinator of the WHO Global Patient Safety Challenge: Medication Without Harm 2. Take early action to protect patients from harm arising from high-risk situations, polypharmacy and transitions of care. 3. Convene national experts, health system leaders and practitioners to develop guidance and action plans for each of the four domains of the strategic framework: patients and the public health and care workers medicines as products systems and practices. 4. Establish mechanisms, including tools and technologies, to enhance patient awareness and knowledge about medicines and medication use process, and their role in managing their own medications safely. 5. Assess progress regularly. 24 Medication without harm: policy brief References 1. Global patient safety action plan 2021–2030: Towards eliminating avoidable harm in health care. Geneva: World Health Organization; 2021 (https://www.who.int/teams/integrated-health-services/patient-safety/policy/global- patient-safety-action-plan accessed 20 June 2023). 2. Panagioti M, Khan K, Keers RN, Abuzour A, Phipps D, Kontopantelis E et al. Prevalence, severity, and nature of preventable patient harm across medical care settings: Systematic review and meta-analysis. BMJ. 2019;366:I4185. doi: 10.11136/bmj.I4185. 3. Global burden of preventable medication related harm: systematic review. Geneva: World Health Organization; 2023 (Up coming). 4. Hodkinson A, Tyler N, Ashcroft DM, Keers RN, Khan K, Phipps D et al. Preventable medication harm across health care settings: a systematic review and meta-analysis. BMC Med. 2020;18(1):1–3. doi: 10.1186/s12916-020-01774-9. 5. Institute of Medicine (US) Committee on Quality of Health Care in America, Kohn LT, Corrigan JM, Donaldson MS, editors. To err is human: Building a safer health system. Washington DC: National Academies Press; 1999 (https:// www.ncbi.nlm.nih.gov/books/NBK225182/ accessed 6 June 2023). 6. Jha AK, Larizgoitia I, Audera-Lopez C, Prasopa-Plaizier N, Waters H, Bates DW. The global burden of unsafe medical care: Analytic modelling of observational studies. BMJ Qual Saf. 2013;22(10):809–15. doi: 10.1136/ bmjqs-2012-001748. 7. Aitken M, Gorokhovich L. Advancing the responsible use of medicines: Applying levers for change. 17 September 2012. SSRN (https://papers.ssrn.com/sol3/papers.cfm?abstract_id=2222541 accessed 6 June 2023). 8. de Bienassis, K., et al. (2022), “The economics of medication safety: Improving medication safety through collective, real-time learning”, OECD Health Working Papers, No. 147, OECD Publishing, Paris, https://ecamet.eu/ wp-content/uploads/2022/09/9a933261-en.pdf Accessed 20 May 2023). 9. Donaldson LJ, Kelley ET, Dhingra-Kumar N, Kieny MP, Sheikh A. Medication without harm: WHO’s third global patient safety challenge. Lancet. 2017;29;389(10080):1680–1 doi: 10.1016/S0140-6736(17)31047-4. 10. Medication without harm. Geneva: World Health Organization; 2017 (https://www.who.int/initiatives/ medication-without-harm accessed 6 June 2023). 11. World Health Organization announcing World Patient Safety Day 2022 (https://www.who.int/campaigns/world- patient-safety-day/2022#:~:text=The%20Jet%20d%27Eau%20in,and%20promote%20safer%20medication%20 use. accessed 6 June 2023). 12. Bates DW, Boyle DL, Vander Vliet MB, Schneider J, Leape L. Relationship between medication errors and adverse drug events. J Gen Intern Med. 1995;10(4):199–205. https://www.ncbi.nlm.nih.gov/pubmed/7790981 13. The importance of pharmacovigilance: safety monitoring of medicinal products. Geneva: World Health Organization; 2002 (https://iris.who.int/handle/10665/42493 accessed 22 September 2023). 14. About medication errors: National Coordinating Council for Medication Error Reporting and Prevention; 2019 (https://www.nccmerp.org/about-medication-errors, accessed 30 May 2023). 15. Conceptual framework for the international classification for patient safety version 1.1: final technical report January 2009. World Health Organization. https://apps.who.int/iris/handle/10665/70882 accessed 3 June 2023. References 25 16. Otero MJ, Schmitt E. Clarifying terminology for adverse drug events. Ann Intern Med. 2005;142(1):77. doi: 10.7326/0003-4819-142-1-200501040-00016. 17. James PB, Wardle J, Steel A, Adams J. Traditional, complementary and alternative medicine use in Sub-Saharan Africa: a systematic review. BMJ global health. 2018 Oct 1;3(5):e000895. doi:10.1136/ bmjgh-2018-000895. 18. Lewis PJ, Dornan T, Taylor D, Tully MP, Wass V, Ashcroft DM. Prevalence, incidence and nature of prescribing errors in hospital inpatients. Drug Saf. 2009;32(5):379–89. doi: 10.2165/00002018-200932050-00002. 19. Elliott RA, Camacho E, Jankovic D, Sculpher MJ, Faria R. Economic analysis of the prevalence and clinical and economic burden of medication error in England. BMJ Qual Saf. 2020;30(2) doi: 10.1136/bmjqs-2019-010206. 20. Alsulami Z, Conroy S, Choonara I. Medication errors in the Middle East countries: A systematic review of the literature. Eur J Clin Pharmacol. 2013;69(4):995–1008 doi: 10.1007/s00228-012-1435-y. 21. Salmasi S, Khan TM, Hong YH, Ming LC, Wong TW. Medication errors in the Southeast Asian countries: A systematic review. PloS One. 2015;10(9):e0136545 doi: 10.1371/journal.pone.0136545. 22. Simegn W, Weldegerima B, Seid M, Zewdie A, Wondimsigegn D, Abyu C, Kasahun AE, Seid AM, Sisay G, Yeshaw Y. Assessment of prescribing errors reported by community pharmacy professionals. J Pharm Policy Pract. 2022 Oct 15;15(1):62. doi: 10.1186/s40545-022-00461-9. 23. Albarrak AI, Al Rashidi EA, Fatani RK, Al Ageel SI, Mohammed R. Assessment of legibility and completeness of handwritten and electronic prescriptions. Saudi Pharm J. 2014;22(6):522–7 doi: 10.1016/j.jsps.2014.02.013. 24. Vigneshwaran E, Sadiq MM, Prathima V. Assessment of completeness and legibility of prescriptions received at community pharmacies. J Health Res Rev. 2016;3(2):72 doi: 10.4103/2394-2010.184242. 25. Fahimi F, Abbasi NM, Abrishami R, Sistanizad M, Mazidi T, Faghihi T et al. Transcription errors observed in a teaching hospital. Arch Iran Med. 2009;12(2):173–5 (PMID: 19249889). 26. Shawahna, R., Abbas, A. & Ghanem, A. Medication transcription errors in hospitalized patient settings: a consensual study in the Palestinian nursing practice. BMC Health Serv Res 19, 644 (2019). https://doi.org/10.1186/s12913-019-4485-3 27. Tulner LR, Kuper IMJA, Frankfort SV, van Campen JPCM, Koks CHW, Branjes DPM et al. Discrepancies in reported drug use in geriatric outpatients: Relevance to adverse events and drug-drug interactions. Am J Geriatr Pharmacother. 2009;7:93–104. doi: 10.1016/j.amjopharm.2009.04.006. 28. Aldhwaihi K, Schifano F, Pezzolesi C, Umaru N. A systematic review of the nature of dispensing errors in hospital pharmacies. Integr Pharm Res Pract. 2016;5:1. doi: 10.2147/IPRP.S95733. 29. Poole SG, Kwong E, Mok B, Mulqueeny B, Yi M, Percival MA. Interventions to decrease the incidence of dispensing errors in hospital pharmacy: A systematic review and meta‐analysis. J Pharm Pract Res. 2021;51(1): 7–21. doi: 10.1002/jppr.1709. 30. Berdot S, Gillaizeau F, Caruba T, Prognon P, Durieux P, Sabatier B. Drug administration errors in hospital inpatients: A systematic review. PloS One. 2013;8(6):e68856 doi: 10.1371/journal.pone.0068856. 31. Slawomirski L, Auraaen A, Klazinga N. The economics of patient safety: Strengthening a value-based approach to reducing patient harm at national level (OECD Health Working Papers No. 96). Paris: Organization for Economic Co-operation and Development; 2017 (https://www.oecd-ilibrary.org/social-issues-migration-health/ the-economics-of-patient-safety_5a9858cd-en accessed 6 June 2023). 32. National Academies of Sciences, Engineering, and Medicine, Health and Medicine Division, Board on Health Care Services, Board on Global Health, Committee on Improving the Quality of Health Care Globally. Crossing the global quality chasm: Improving health care worldwide. Washington DC: National Academies Press; 2018 (https://pubmed.ncbi.nlm.nih.gov/30605296/ accessed 6 June 2023). 33. Slawomirski L, Auraaen A, Klazinga N. The economics of patient safety in primary and ambulatory care: Flying blind (OECD Health Working Papers No. 106). Paris: Organization for Economic Co-operation and Development; 2018 (https://www.oecd-ilibrary.org/social-issues-migration-health/the-economics-of-patient-safety-in- primary-and-ambulatory-care_baf425ad-en accessed 6 June 2023). 34. Kristensen S, Burtscher M, Brownwood I, Klazinga NS. Culture as a cure: Assessments of patient safety culture in OECD countries (OECD Health Working Papers 119); Paris: Organization for Economic Co-operation and Development (https://www.oecd.org/health/culture-as-a-cure-6ee1aeae-en.htm accessed 6 June 2023). 26 Medication without harm: policy brief 35. Assiri GA, Shebl NA, Mahmoud MA, Aloudah N, Grant E, Aljadhey H et al. What is the epidemiology of medication errors, error-related adverse events and risk factors for errors in adults managed in community care contexts? A systematic review of the international literature. BMJ open. 2018;8(5):e019101. doi: 10.1136/ bmjopen-2017-019101. 36. Elliott RA, Camacho E, Campbell F, Jankovic D, Martyn-St James M, Kaltenthaler E et al. Prevalence and Economic Burden of Medication Errors in The NHS in England: Rapid evidence synthesis and economic analysis of the prevalence and burden of medication error in the UK. Policy Research Unit in Economic Evaluation of Health and Care Interventions (EEPRU), 2018 (https://pure.york.ac.uk/portal/en/publications/prevalence-and-economic- burden-of-medication-errors-in-the-nhs-in accessed 6 June 2023). 37. Insani WN, Whittlesea C, Alwafi H, Man KK, Chapman S, Wei L. Prevalence of adverse drug reactions in the primary care setting: A systematic review and meta-analysis. PLoS One. 2021;16(5):e0252161. doi: 10.1371/ journal.pone.0252161. 38. Avery AJ, Ghaleb M, Barber N, Dean Franklin B, Armstrong SJ, Serumaga B, Dhillon S, Freyer A, Howard R, Talabi O, Mehta RL. The prevalence and nature of prescribing and monitoring errors in English general practice: a retrospective case note review. Br J Gen Pract. 2013 Aug;63(613):e543-53. doi: 10.3399/bjgp13X670679. 39. Wilson RM, Michel P, Olsen S, Gibberd RW, Vincent C, El-Assady R et al. Patient safety in developing countries: Retrospective estimation of scale and nature of harm to patients in hospital. BMJ. 2012;344:e832. doi: 10.1136/ bmj.e832. 40. Kongkaew C, Hann M, Mandal J, Williams SD, Metcalfe D, Noyce PR et al. Risk factors for hospital admissions associated with adverse drug events. Pharmacotherapy. 2013;33(8):827–37 doi: 10.1002/phar.1287. 41. Suggett E, Marriott J. Risk factors associated with the requirement for pharmaceutical intervention in the hospital setting: A systematic review of the literature. Drugs Real World outcomes. 2016;3(3):241–63. doi: 10.1007/s40801-016-0083-4. 42. Ghaleb MA, Barber N, Franklin BD, Yeung VW, Khaki ZF, Wong IC. Systematic review of medication errors in pediatric patients. The Annals of Pharmacotherapy 2006;40:1766‐76. DOI: 10.1345/aph.1G717 43. Lafortune G, Balestat G. Trends in severe disability among elderly people: Assessing the evidence in 12 OECD countries and the future implications (OECD Working Papers 26) (https://www.oecd-ilibrary.org/social-issues- migration-health/trends-in-severe-disability-among-elderly-people_217072070078 accessed 6 June 2023). 44. Karandikar YS, Chaudhari SR, Dalal NP, Sharma M, Pandit VA. Inappropriate prescribing in the elderly: A comparison of two validated screening tools. J Clin Gerontol Geriatr. 2013;4(4):109–14. doi: 10.1016/j. jcgg.2013.04.004. 45. Virnes RE, Tiihonen M, Karttunen N, van Poelgeest EP, van der Velde N, Hartikainen S. Opioids and falls risk in older adults: A narrative review. Drugs Aging. 2022:1–9. doi: 10.1007/s40266-022-00929-y. 46. Cameron EJ, Bowles SK, Marshall EG, Andrew MK. Falls and long-term care: A report from the care by design observational cohort study. BMC Fam Pract. 2018;19(1):1–7. doi: 10.1186/s12875-018-0741-6. 47. Seppala LJ, van de Glind EM, Daams JG, Ploegmakers KJ, de Vries M, Wermelink AM et al. Fall-risk-increasing drugs: A systematic review and meta-analysis: III. Others. J Am Med Dir Assoc. 2018;19(4):372.e1–8. doi: 10.1016/j.jamda.2017.12.099. 48. Roh HW, Lee DE, Lee Y, Son SJ, Hong CH. Gender differences in the effect of depression and cognitive impairment on risk of falls among community-dwelling older adults. J Affect Disorders. 2021;282:504–10. doi: 10.1016/j.jad.2020.12.170. 49. Leelakanok N, D’Cunha RR. Association between polypharmacy and dementia – A systematic review and metaanalysis. Aging Mental Health. 2019;23(8):932–41. doi: 10.1080/13607863.2018.1468411. 50. Barnett K, Mercer SW, Norbury M, Watt G, Wyke S, Guthrie B. Epidemiology of multimorbidity and implications for health care, research, and medical education: A cross‐sectional study. Lancet. 2012;380:37–43. doi: 10.1016/ S0140-6736(12)60240-2. 51. Cassell A, Edwards D, Harshfield A, Rhodes K, Brimicombe J et al. The epidemiology of multimorbidity in primary care: A retrospective cohort study. Br J Gen Pract. 2018;68:e245–51. doi: 10.3399/bjgp18X695465. 52. Panagioti M, Stokes J, Esmail A, Coventry P, Cheraghi-Sohi S, Alam R et al. Multimorbidity and patient safety incidents in primary care: A systematic review and meta-analysis. PloS One. 2015;10(8):e0135947. doi: 10.1371/ journal.pone,0135947. References 27 53. Köberlein J, Jürges H. Multimorbidity, incentives and the use of health services in Europe. Chapter 21. Börsch- Supan A, Brandt M, Litwin H, Weber G, editors. Active ageing and solidarity between generations in Europe. Boston (MA): De Gruyter; 2013:243–52 (doi: 10.1515/9783110295467.243). 54. Benetos A, Rossignol P, Cherubini A, Joly L, Grodzicki T, Rajkumar C et al. Polypharmacy in the aging patient: Management of hypertension in octogenarians. JAMA. 2015;314(2):170–80 (doi: 10.1001/jama.2015.7517). 55. Hansen ML, Sørensen R, Clausen MT, Fog-Petersen ML, Raunsø J, Gadsbøll N et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med. 2010;170(16):1433–41. doi: 10.1001/archinternmed.2010.271. 56. Gutiérrez‐Valencia M, Izquierdo M, Cesari M, Casas‐Herrero Á, Inzitari M, Martínez‐Velilla N. The relationship between frailty and polypharmacy in older people: A systematic review. Br J Clin Pharmacol. 2018;84(7):1432– 44. doi: 10.1111/bcp.13590. 57. Bonaga B, Sánchez-Jurado PM, Martínez-Reig M, Ariza G, Rodríguez-Mañas L, Gnjidic D et al. Frailty, polypharmacy, and health outcomes in older adults: The frailty and dependence in Albacete study. J Am Med Dir Assoc. 2018;19(1):46–52. doi: 10.1016/j.jamda.2017.008. 58. Liu HX, Ding G, Yu WJ, Liu TF, Yan AY, Chen HY et al. Association between frailty and incident risk of disability in community-dwelling elder people: Evidence from a meta-analysis. Public Health. 2019;175:90–100. doi: 10.1016/ puhe.2019.06.010. 59. Medication safety in polypharmacy: Technical report. Geneva: World Health Organization; 2019 (https://iris.who. int/bitstream/handle/10665/325454/WHO-UHC-SDS-2019.11-eng.pdf?sequence=1, accessed 3 June 2023). 60. Masnoon, N., Shakib, S., Kalisch-Ellett, L. et al. What is polypharmacy? A systematic review of definitions. BMC Geriatr 17, 230 (2017). https://doi.org/10.1186/s12877-017-0621-2. 61. Guthrie B, Payne K, Alderson P, McMurdo ME, Mercer SW. Adapting clinical guidelines to take account of multimorbidity. BMJ. 2012;345:e6341. doi: 10.1136/bmj.e6341. 62. Multimorbidity. Technical series on safer primary care. Geneva: World Health Organization; 2016 (https://www.who.int/publications/i/item/9789241511650, accessed 3 June 2023). 63. Smith SM, Soubhi H, Fortin M, Hudon C, O’Dowd T. Managing patients with multimorbidity: Systematic review of interventions in primary care and community settings. BMJ. 2012;345:e5205. doi: 10.1136/bmj.e5205. 64. Medication safety in high-risk situations. Geneva: World Health Organization; 2019 (https://iris.who.int/ bitstream/handle/10665/325131/WHO-UHC-SDS-2019.10-eng.pdf?sequence=1, accessed 6 June 2023). 65. ISMP list of high-alert medications in acute care settings. Plymouth Meeting (PA): Institute for Safe Medication Practices; 2018 (https://www.ismp.org/recommendations/high-alert-medications-acute-list accessed 6 June 2023). 66. Alanazi MA, Tully MP, Lewis PJ. A systematic review of the prevalence and incidence of prescribing errors with high‐risk medicines in hospitals. J Clin Pharm Ther. 2016;41(3):239–45. doi: 10.111/cpt.12389. 67. ISMP list of high-alert medications in community/ambulatory care settings. Plymouth Meeting (PA): Institute for Safe Medication Practices; 2018 (https://www.ismp.org/recommendations/high-alert-medications-community- ambulatory-list accessed 6 June 2023). 68. Sustaining Action Against Antimicrobial Resistance: A Case Series of Country Experiences]. Washington, DC: World Bank and the World Health Organization; [2022]. License: CC BY 3.0 IGO. (https://openknowledge. worldbank.org/bitstream/handle/10986/38162/IDU0f31c164b04ee504108082d70c62e2f642357. pdf?sequence=1&isAllowed=y, accessed 6 June 2023). 69. Murray CJ, Ikuta KS, Sharara F, Swetschinski L, Aguilar GR, Gray A, Han C, Bisignano C, Rao P, Wool E, Johnson SC. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet. 2022 Feb 12;399(10325):629-55. https://doi.org/10.1016/S0140-6736(21)02724-0. 70. Global antimicrobial resistance and use surveillance system (GLASS) report 2021. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO. (https://apps.who.int/iris/handle/10665/341666, accessed 6 June 2023). 71. Tamma PD, Avdic E, Li DX, Dzintars K, Cosgrove SE. Association of adverse events with antibiotic use in hospitalized patients. JAMA Intern Med. 2017;177(9):1308–15. doi: 10.1001/jamainternmed.2017.1938. 72. Dietz I, Borasio GD, Schneider G, Jox RJ. Medical errors and patient safety in palliative care: A review of current literature. J Palliat Med. 2010;13(12):1469–74. doi: 10.1089/jpm.2010.0228. 28 Medication without harm: policy brief 73. Heneka N, Shaw T, Rowett D, Lapkin S, Phillips JL. Opioid errors in inpatient palliative care services: A retrospective review. BMJ Support Palliat Care. 2018;8(2):175–9. doi: 10.1136/bmjspcare-2017-001417. 74. Heneka N, Shaw T, Rowett D, Phillips JL. Quantifying the burden of opioid medication errors in adult oncology and palliative care settings: A systematic review. Palliat Med. 2016;30(6):520–32. doi: 10.1177/0269216315615002. 75. Medication safety in transitions of care: Technical report. Geneva: World Health Organization; 2019 (https://apps.who.int/iris/handle/10665/325453 accessed 6 June 2023). 76. Redmond P, Grimes TC, McDonnell R, Boland F, Hughes C, Fahey T. Impact of medication reconciliation for improving transitions of care. Cochrane Database Syst Rev. 2018;8(8):CD010791.doi: 10.1002/14651858. CD01791.pub2. 77. Glintborg B, Andersen SE, Dalhoff K. Insufficient communication about medication use at the interface between hospital and primary care. BMJ Qual Saf. 2007;16(1):34–9. doi: 10.1136/qshc.2006.019828. 78. Alqenae FA, Steinke D, Keers RN. Prevalence and nature of medication errors and medication-related harm following discharge from hospital to community settings: A systematic review. Drug Saf. 2020;43(6):517–37. https://doi.org/10.1007/s40264-020-00918-3. 79. Becerra-Camargo J, Martinez-Martinez F, Garcia-Jimenez E. A multicentre, double-blind, randomised, controlled, parallel-group study of the effectiveness of a pharmacist-acquired medication history in an emergency department. BMC Health Serv Res. 2013;13(1):1–2. doi: 10.1186/1472-6963-13-337. 80. Zarif-Yeganeh M, Rastegarpanah M, Garmaroudi G, Hadjibabaie M, Vahedi HS. Incidence of medication discrepancies and its predicting factors in emergency department. Iran J Public Health. 2017;46(8):1086 (PMID: 28894710). 81. Tamiru A, Edessa D, Sisay M, Mengistu G. Magnitude and factors associated with medication discrepancies identified through medication reconciliation at care transitions of a tertiary hospital in eastern Ethiopia. BMC Res Notes. 2018;11(1):1–7. doi: 1186/s13104-018-3668-z. 82. Ozawa S, Evans DR, Bessias S, Haynie DG, Yemeke TT, Laing SK et al. Prevalence and estimated economic burden of substandard and falsified medicines in low-and middle-income countries: A systematic review and meta- analysis. JAMA Netw Open. 2018;1(4):e181662. doi: 10.1001/jamanetworkopen.2018.1662. 83. Trends in trade in counterfeit and pirated goods. Paris; Organization for Economic Co-operation and Development; 2019 (https://www.oecd.org/corruption-integrity/reports/trends-in-trade-in-counterfeit-and- pirated-goods-g2g9f533-en.html, accessed 6 June 2023). 84. Substandard and falsified medical products. Fact sheet. Geneva: World Health Organization; 2018 (https://www. who.int/news-room/fact-sheets/detail/substandard-and-falsified-medical-products accessed 6 June 2023). 85. The WHO Member State mechanism on substandard and falsified medical products. Geneva: World Health Organization; 2020 (https://www.who.int/publications/i/item/WHO-MVP-EMP-SAV-2019.04 accessed 6 June 2023). 86. Medication safety for look-alike, sound-alike medicines. Geneva: World Health Organization; 2023. Licence: https://iris.who.int/bitstream/handle/10665/373495/9789240058897-eng.pdf?sequence=1, accessed 10 December 2023). 87. Bryan R, Aronson JK, Williams A, Jordan S. The problem of look-alike sound alike name errors: Drivers and solutions. Br J Clin Pharmacol. 2020;87(2):386–94. doi: 10.1111/bcp.14285. 88. Look-alike drug names with recommended tall man letters. United States Food and Drug Administration and Institute for Safe Medication Practices; 2016 (https://www.ismp.org/recommendations/tall-man-letters-list, accessed 6 June 2023). 89. Swift CG. Personalised future prescribing using pharmacogenomics: A resumé of a joint Royal College of Physicians/British Pharmacological Society working party report. Future Healthcare Journal. 2022 Jul;9(2):17 (https://www.rcpjournals.org/content/futurehosp/9/2/174 accessed 6 June 2023). 90. Mao X, Jia P, Zhang L, Zhao P, Chen Y, Zhang M. An evaluation of the effects of human factors and ergonomics on health care and patient safety practices: A systematic review. PloS One. 2015;10(6):e0129948. doi: 10.1371/ journal.pone.0129948. References 29 91. Hodkinson A, Zhou A, Johnson J, Geraghty K, Riley R, Zhou A, Panagopoulou E, Chew-Graham CA, Peters D, Esmail A, Panagioti M. Associations of physician burnout with career engagement and quality of patient care: systematic review and meta-analysis. bmj. 2022 Sep 14;378. https://doi.org/10.1136%2Fbmj-2022-070442. 92. Guo L, Ryan B, Leditschke IA, Haines KJ, Cook K, Eriksson L, Olusanya O, Selak T, Shekar K, Ramanan M. Impact of unacceptable behaviour between healthcare workers on clinical performance and patient outcomes: a systematic review. BMJ quality & safety. 2022 Sep 1;31(9):679-87. https://doi.org/10.1136/bmjqs-2021-013955. 93. Robertson JJ, Long B. Suffering in silence: Medical error and its impact on health care providers. J Emergency Med. 2018;54(4):402–9. doi: 10.1016/j.jemermed.2017.12.001. 94. Edrees HH, Paine LA, Feroli ER, Wu AW. Health care workers as second victims of medical errors. Pol Arch Med Wewn. 2011;121(4):101–8. PMID: 21532531. 95. Sudhinaraset M, Ingram M, Lofthouse HK, Montagu D. What is the role of informal healthcare providers in developing countries? A systematic review. PloS One. 2013;8(2):e54978. doi: 10.1371/journal.pone.0054978. 96. Shore CB, Maben J, Mold F, Winkley K, Cook A, Stenner K. Delegation of medication administration from registered nurses to non-registered support workers in community care settings: A systematic review with critical interpretive synthesis. International Journal of Nursing Studies. 2022 Feb 1;126:104121. doi: 10.1016/j. ijnurstu.2021.104121 97. Boytim J, Ulrich B. Factors contributing to perioperative medication errors: a systematic literature review: 2.1 www. aornjournal. org/content/cme. AORN journal. 2018 Jan;107(1):91-107. https://doi.org/10.1002/aorn.12005 98. Kuitunen S, Niittynen I, Airaksinen M, Holmström AR. Systemic Causes of In-Hospital Intravenous Medication Errors: A Systematic Review. J Patient Saf. 2021 Dec 1;17(8):e1660-e1668. doi: 10.1097/PTS.0000000000000632. 99. Patient safety: Making health care safer. Geneva: World Health Organization; 2017. (https://iris.who.int/ bitstream/handle/10665/255507/WHO-HIS-SDS-2017.11-eng.pdf?sequence=1 accessed 4 June 2023). 100. Reason J. Human error: Models and management. BMJ. 2000;320(7237):768–70. https://doi. org/10.1136%2Fbmj.320.7237.768. 101. lsabri M, Boudi Z, Lauque D, Dias RD, Whelan JS, Östlundh L, Alinier G, Onyeji C, Michel P, Liu SW, Carlos Jr A. Impact of teamwork and communication training interventions on safety culture and patient safety in emergency departments: a systematic review. Journal of Patient Safety. 2022 Jan 1;18(1):e351-61. https://doi.org/10.1097/pts.0000000000000782. 102. Reporting and learning systems for medication errors: The role of pharmacovigilance centres. Geneva: World Health Organization; 2017 (https://apps.who.int/iris/handle/10665/137036 accessed 6 June 2023). 103. Cousins DH, Gerrett D, Warner B. A review of medication incidents reported to the National Reporting and Learning System in England and Wales over six years (2005–2010). Br J Clin Pharm. 2012;74:597–604. doi: 10.1111/j.1365-2125.2011.04166.x. 104. Goedecke T, Ord K, Newbould V, Brosch S, Arlett P. Medication errors: New EU good practice guide on risk minimisation and error prevention. Drug Saf. 2016;39(6):491–500 doi: 10.1007/s40264-016-0410-4. 105. Olsson S, Pal SN, Dodoo A. Pharmacovigilance in resource-limited countries. Expert review of clinical pharmacology. 2015 Jul 4;8(4):449-60. https://doi.org/10.1586/17512433.2015.1053391. 106. National safety and quality health service standards (second edition). Sydney: Australian Commission on Safety and Quality in Health Care; 2012 (https://www.safetyandquality.gov.au/sites/default/files/migrated/National- Safety-and-Quality-Health-Service-Standards-second-edition.pdf accessed 6 June 2023). 107. Manias E, Kusljic S, Wu A. Interventions to reduce medication errors in adult medical and surgical settings: A systematic review. Ther Adv Drug Saf. 2020;11:2042098620968309. doi: 10.1177/.2042098620968309. 108. Coombes ID, Reid C, McDougall D, Stowasser D, Duiguid M, Mitchell C. Pilot of a national inpatient medication chart in Australia: Improving prescribing safety and enabling prescribing training. Br J Clin Pharmacol. 2011;72(2):338–49. doi: 1111/j.1365-2125.2011.03967.x. 109. McNab D, Bowie P, Ross A, MacWalter G, Ryan M, Morrison J. Systematic review and meta-analysis of the effectiveness of pharmacist-led medication reconciliation in the community after hospital discharge. BMJ Qual Saf. 2018;27(4):308–20. doi: 10.1136/bmjqs-2017-007087. 30 Medication without harm: policy brief 110. Royal S, Smeaton L, Avery AJ, Hurwitz B, Sheikh A. Interventions in primary care to reduce medication related adverse events and hospital admissions: Systematic review and meta-analysis. BMJ Qual Saf. 2006;15(1):23–31. doi: 10.1136/qshc.2004.012153. 111. Ali S, Salahudeen MS, Bereznicki LR, Curtain CM. Pharmacist‐led interventions to reduce adverse drug events in older people living in residential aged care facilities: A systematic review. Br J Clin Pharmacol. 2021;87(10):3672– 89. doi: 10.1111/bcp.14824. 112. Scott IA, Hilmer SN, Reeve E, Potter K, Couteur DL, Rigby D et al. Reducing inappropriate polypharmacy: The process of deprescribing. JAMA Intern Med. 2015;175(5):827–34. doi: 10.1001/jamainternmed.2015.0324. 113. O’Mahony D, O’Sullivan D, Byrne S, O’Connor MN, Ryan C, Gallagher P. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing. 2015;44(2):213–8. doi: 10.1092/ageing/afu145. 114. Recommendations to enhance accuracy of prescription/medication order writing. Villa Park (IL): National Coordinating Council for Medication Error Reporting and Prevention; 2014 (https://www.nccmerp.org/ recommendations-enhance-accuracy-prescription-writing, accessed 6 June 2023). 115. Stewart D, Mair A, Wilson M, Kardas P, Lewek P, Alonso A et al. Guidance to manage inappropriate polypharmacy in older people: Systematic review and future developments. Expert Opin Drug Saf. 2017;16(2):203–13. doi: 10.1080/14740338.2017.1265503. 116. Chiewchantanakit D, Meakchai A, Pituchaturont N, Dilokthornsakul P, Dhippayom T. The effectiveness of medication reconciliation to prevent medication error: A systematic review and meta-analysis. Res Soc Admin Pharm. 2020;16(7):886–94. doi: 10.1016/j.sapharm.2019.10.004. 117. Bourne RS, Jennings JK, Panagioti M, Hodkinson A, Sutton A, Ashcroft DM. Medication-related interventions to improve medication safety and patient outcomes on transition from adult intensive care settings: a systematic review and meta-analysis. BMJ Quality & Safety. 2022 Aug 1;31(8):609-22. DOI: 10.1136/bmjqs-2021-013760. 118. Avery AJ, Rodgers S, Cantrill JA, Armstrong S, Cresswell K, Eden M et al. A pharmacist-led information technology intervention for medication errors (PINCER): A multicentre, cluster randomised, controlled trial and cost-effectiveness analysis. Lancet. 2012;379(9823):1310–9. doi: 10.1016/S0140-6736(11)61817-5. 119. Exploring patient participation in reducing health-care-related safety risks. Geneva: World Health Organization; 2013 (https://apps.who.int/iris/bitstream/handle/10665/326442/9789289002943-eng.pdf accessed 6 June 2023). 120. Know Check Ask. Geneva: World Health Organization; 2022 (https://www.who.int/initiatives/medication-without-harm/campaign-materials accessed 3 June 2023). 121. Five moments of medication safety. Geneva: World Health Organization; 2019 (https://iris.who.int/bitstream/ handle/10665/311153/WHO-HIS-SDS-2019.4-eng.pdf?sequence=1, accessed 3 June 2023). 122. Heekin AM, Kontor J, Sax HC, Keller MS, Wellington A, Weingarten S. Choosing wisely clinical decision support adherence and associated inpatient outcomes. Am J Managed Care. 2018;24(8):361. PMID: 30130028. 123. Five questions to ask about your medications. Torinto (Ont): ISMP Canada (https://www.ismp-canada.org/medrec/5questions.htm, accessed 3 June 2023). 124. Bombard Y, Baker GR, Orlando E, Fancott C, Bhatia P, Casalino S et al. Engaging patients to improve quality of care: A systematic review. Implement Sci. 2018;13(1):1–22. doi: 10.1186/s13012-018-0784-z. 125. Garfield S, Furniss D, Husson F, Etkind M, Williams M, Norton J et al. How can patient-held lists of medication enhance patient safety? A mixed-methods study with a focus on user experience. BMJ Qual Saf. 2020;29(9):764– 73. doi: 10.1136/bmjqs-2019-010194. 126. Barber S, Thakkar K, Marvin V, Franklin BD, Bell D. Evaluation of My Medication Passport: A patient-completed aide-memoire designed by patients, for patients, to help towards medicines optimisation. BMJ Open. 2014;4(8):e005608. doi: 10.1136/bmjopen-2014-005608. 127. O’Donovan B, Kirke C, Pate M, McHugh SM, Bennett KE, Cahir C. “Everyone should know what they’re on”: A qualitative study of attitudes towards and use of patient held lists of medicines among patients, carers and healthcare professionals in primary and secondary care settings in Ireland. BMJ Open. 2022;12(7):e064484. doi: 10.1136/bmjopen-2022-064484. 128. Patient safety curriculum guide: multi-professional edition. Geneva: World Health Organization; 2011 (https:// www.who.int/publications/i/item/9789241501958 accessed 6 June 2023). References 31 129. International Union of Basic and Clinical Pharmacology, Council for International Organization of Medical Sciences. World Health Organisation, Clinical pharmacology in healthcare teaching and research 2012. (https://cioms.ch/publications/product/clinical-pharmacology-in-health-care-teaching-and-research/ Accessed 6 September 2023). 130. WHO Prequalification of Medicines Programme. WHO Drug Inf. 2013;27(4):325–31 (https://apps.who.int/iris/ bitstream/handle/10665/331154/DI274-325-331-eng.pdf?sequence=1&isAllowed=y accessed 6 June 2023). 131. Coyne PE. The World Health Organization prequalification programme – Playing an essential role in assuring quality medical products. Int Health. 2019;11(2):79–80. doi: 10.1093/inthealth/ihy095. 132. WHO global surveillance and monitoring system for substandard and falsified medical products. Geneva: World Health Organization; 2017 (https://apps.who.int/iris/handle/10665/326708 accessed 6 June 2023). 133. World Health Organization Model Lists of Essential Medicines https://www.who.int/groups/expert-committee- on-selection-and-use-of-essential-medicines/essential-medicines-lists accessed 8 December 2023). 134. Choosing Wisely®. Philadelphia (PA): American Board of Internal Medicine Foundation; 2021 (https://www.choosingwisely.org/wpcontent/uploads/2021/05/ASCP_10things_List.pdf, accessed 3 June 2023). 135. Ammenwerth E, Schnell-Inderst P, Machan C, Siebert U. The effect of electronic prescribing on medication errors and adverse drug events: A systematic review. J Am Med Informatics Assoc. 2008;15(5):585–600. doi: 10.1197/ jamia.M2667. 136. Slight SP, Tolley CL, Bates DW, Fraser R, Bigirumurame T, Kasim A et al. Medication errors and adverse drug events in a UK hospital during the optimisation of electronic prescriptions: A prospective observational study. Lancet Digital Health. 2019;1(8):e403–12. doi: 10.1016/S2589-7500(19)30158-X. 137. Hutton K, Ding Q, Wellman G. The effects of bar-coding technology on medication errors: A systematic literature review. J Patient Saf. 2021;17(3):e192–206. doi: 10.1097/PTS.0000000000000366. 138. Jessurun JG, Hunfeld NG, Van Rosmalen J, Van Dijk M, Van Den Bemt PM. Effect of automated unit dose dispensing with barcode scanning on medication administration errors: An uncontrolled before-and-after study. Int J Qual Health Care. 2021;33(4):mzab142. doi: 10.1093/intqhc/mzab142. 139. Jessurun JG, Hunfeld NG, van Dijk M, Polinder S. Cost-effectiveness of central automated unit dose dispensing with barcode-assisted medication administration in a hospital setting. Res Soc Admin Pharm. 2022. doi:10.1093/ intqhc/mzab142. 140. Khalil H, Kynoch K, Hines S. Interventions to ensure medication safety in acute care: An umbrella review. JBI Evidence Implement. 2020;18(2):188–211. doi: 10.1097/XEB.0000000000000232. 141. Cajanding JMR. Administering and monitoring high-alert medications in acute care. Nurs Stand. 2017 Jul 19;31(47):42-52. doi: 10.7748/ns.2017.e10849. PMID: 2872179. 142. Weant KA, Bailey AM, Baker SN. Strategies for reducing medication errors in the emergency department. Open access Emergency Med. 2014;6:45. doi: 10.2147/OAEM.S64174. 143. Chen Y, Wu X, Huang Z, Lin W, Li Y, Yang J, Li J. Evaluation of a medication error monitoring system to reduce the incidence of medication errors in a clinical setting. Research in Social and Administrative Pharmacy. 2019 Jul 1;15(7):883-8. DOI: 10.1016/j.sapharm.2019.02.006. 32 Medication without harm: policy brief Annexes Annex 1: Glossary Term Definition and source Adverse drug event Any injury resulting from medical interventions with a drug, including both adverse drug reactions in which no error occurred and complications resulting from medication errors (1) Adverse drug reaction A response to a drug that is noxious and unintended and that occurs at doses used in humans for prophylaxis, diagnosis or therapy of diseases or to modify physiological function (2). These are often classified as Type A or Type B (3): Type A adverse drug reaction: An augmented pharmacologically predictable reaction that is dose dependent; generally associated with high morbidity and low mortality (4) Type B adverse drug reaction: A bizarre reaction that is unpredictable pharmacologically and is independent of dose; generally associated with low morbidity and high mortality (4) Anaphylaxis A severe, life-threatening systemic hypersensitivity reaction characterized by rapid onset with potentially life-threatening effects on the airway, breathing or circulatory system; usually, although not always, associated with skin and mucosal changes (5) Best possible medication history A medication history obtained by a clinician that includes a thorough history of all regular medication use (prescribed and non-prescribed) from a number of sources of information (6) De-prescribing Tapering off, stopping, discontinuing or withdrawing drugs in order to manage polypharmacy and improve outcomes (7) Essential medicine Essential medicines are those that satisfy the priority health care needs of the population (8) Forcing function An aspect of design that prevents the user from acting without consciously considering information relevant to the action; forces conscious attention (“bringing to consciousness”) and thus deliberately disrupts efficient or automatized performance of a task (9) Formulary A list of medicines, usually by their generic names, and indications for their use. A formulary is intended to include a sufficient range of medicines to enable medical practitioners, dentists and, as appropriate, other practitioners to prescribe all medically appropriate treatment for all reasonably common illnesses (10). High-risk (high-alert) medications Drugs that heighten the risk of significant patient harm when they are used erroneously. Although mistakes may or may not be more common with these medications, the consequences of an error are clearly more devastating to patients (11). Medication adherence The degree to which use of a medication by a patient corresponds to the prescribed regimen (12) Annexes 33 Term Definition and source Medication discrepancy Any difference between medication use history and admission medication orders (13); may be intentional, undocumented intentional or unintentional (6) Medication error Any preventable event that causes or leads to inappropriate medication use or patient harm while the medication is under the control of a health care professional, patient or consumer. Such events may be related to professional practice, healthcare products, procedures, and systems, including prescribing, order communication, product labelling, packaging and nomenclature, compounding, dispensing, distribution, administration, education, monitoring, and use (14) Medication reconciliation Formal process in which health care professionals form partnerships with patients to ensure accurate, complete medication information transfer at interfaces of care (6) Medication-related harm Patient harm related to medication, including preventable adverse drug events (e.g., due to a medication error or accidental or intentional misuse) and nonpreventable adverse drug events (e.g., an adverse drug reaction) Medication review A structured evaluation of a patient’s medicines with the aim of optimizing their use and improving health outcomes; entails detecting drug-related problems and recommending interventions (15) Medication safety Absence of accidental injury during the course of medication use; activities to avoid, prevent or correct adverse drug events that may result from use of medications (16) Medication use process The multistep process of use of medications by or for patients, including prescribing, ordering, storage, dispensing, preparing, administering and/or monitoring Medicines optimization Ensuring that the right patient receives the right medicine at the right time by focusing on patients and their experiences, to help patients to (a) improve their outcomes, (b) take their medicines correctly, (c) avoid taking unnecessary medicines, (d) reduce wastage of medicines and (e) improve the safety of medicines (17) Multimorbidity The presence of two or more long-term health conditions, which may include (a) defined physical and mental health conditions such as diabetes and schizophrenia; (b) ongoing conditions such as learning disability; (c) symptom complexes such as frailty or chronic pain; (d) sensory impairment such as sight or hearing loss; and (e) alcohol or substance misuse (18) Near miss An incident that did not affect the patient (19) Patient safety The absence of preventable harm to a patient and reduction of risk of unnecessary harm associated with health care to an acceptable minimum. An acceptable minimum refers to the collective notions of given current knowledge, resources available and the context in which care was delivered weighed against the risk of non-treatment or other treatment (20) Pharmacovigilance Science and activities for the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem (2) Polypharmacy Concurrent use of several medications, often defined as routine use of five or more medications (21), including over-the-counter, prescription and/or traditional and complementary medicines Potentially inappropriate medication Medications that are ineffective or have a high risk–benefit ratio for a particular individual or group of individuals (22) Safety Reduction of the risk of unnecessary harm to an acceptable minimum (19) Side-effect A known effect, other than that primarily intended, related to the pharmacological properties of a medication (19) Transitions of care The various points where a patient moves to, or returns from, a particular physical location or makes contact with a health care professional for the purposes of receiving health care (23) 34 Medication without harm: policy brief Glossary references 1. Bates DW, Boyle DL, Vander Vliet MB, Schneider J, Leape L. Relationship between medication errors and adverse drug events. J Gen Intern Med. 1995;10(4):199–205 doi: 10.1007/BF02600255. 2. The importance of pharmacovigilance: safety monitoring of medicinal products. Geneva: World Health Organization; 2002 (https://www.who.int/publications/i/item/10665-42493, accessed 6 June 2023). 3. Yellow card scheme. Guidance on adverse drug reactions. London: Medicines and Healthcare Products Regulatory Agency; 2019 (https://www.gov.uk/guidance/the-yellow-card-scheme-guidance-for-healthcare- professionals, accessed 6 June 2023). 4. Rawlins M. Drug safety: A shared responsibility. Edinburgh: Churchill Livingstone; 1991 Royal Pharmaceutical Society 2001. 5. ICD-11. 4A84 Anaphylaxis. Geneva: World Health Organization; 2018 (https://icd.who.int/browse11/l-m/en#/ http://id.who.int/icd/entity/1868068711 accessed 4 June 2023). 6. The high 5s project implementation guide. Assuring medication accuracy at transitions in care: medication reconciliation. Geneva: World Health Organization; 2014 https://cdn.who.int/media/docs/default-source/ integrated-health-services-(ihs)/psf/high5s/h5s-guide.pdf?sfvrsn=3bbdb46a_4 accessed 6 June 2023). 7. Thomson W, Farrell B. Deprescribing: what is it and what does the evidence tell us? Can J Hosp Pharm. 2013;66(3):201-2. https://doi.org/10.4212/cjhp.v66i3.1261 8. Essential medicines. In: Health topics [website]. Geneva: World Health Organization; 2019 https://www.who.int/ westernpacific/health-topics/essential-medicines accessed 6 June 2023). 9. Forcing functions. In: Interaction Design Foundation [website]. Aarhus: Interaction Design Foundation; 2019 https://www.interaction-design.org/literature/book/the-glossary-of-human-computer-interaction/forcing- functions accessed 6 June 2023). 10. A glossary of terms for community health care and services for older persons. Geneva: World Health Organization; 2004 (https://apps.who.int/iris/handle/10665/68896, accessed 6 June 2023). 11. High-alert medications in community/ambulatory settings. Horsham (PA): Institute for Safe Medication Practices; 2011 (https://www.ismp.org/recommendations/high-alert-medications-community-ambulatory-list, accessed 6 June 2023). 12. Adherence to long-term therapies: evidence for action. Geneva: World Health Organization; 2003. https://apps. who.int/iris/handle/10665/42682, accessed 6 June 2023). 13. Cornish PL, Knowles SR, Marchesano R, Tam V Shadowitz S, Juurlink DN et al. Unintended medication discrepancies at the time of hospital admission. Arch Intern Med. 2005;165:424–9 doi: 10.1001/ archinte.165.4.424. 14. About medication errors. Villa Park (IL): National Coordinating Council for Medication Error Reporting and Prevention; 2019 (https://www.nccmerp.org/about-medication-errors, accessed 6 July 2023). 15. Medication review definition approved [website]. Zuidlaren: Pharmaceutical Care Network Europe; 2019 https:// www.pcne.org/news/35/medication-review-definition-approved, accessed 6 June 2023). 16. Committee of Experts on Management of Safety and Quality in Health Care. Glossary of terms related to patient and medication safety. Strasbourg: Council of Europe; 2005 (http://www.who.int/patientsafety/highlights/COE_ patient_and_medication_safety_gl.pdf, accessed 6 June 2023). 17. Medicines optimisation: Helping patients to make the most of medicine. London: Royal Pharmaceutical Society; 2013 (https://www.rpharms.com/Portals/0/RPS%20document%20library/Open%20access/Policy/helping- patients-make-the-most-of-their-medicines.pdf, accessed 6 June 2023). 18. Multimorbidity: Clinical assessment and management. London: National Institute for Health and Care Excellence; 2016 (https://www.nice.org.uk/guidance/ng56/chapter/Recommendations#general-principles, accessed 6 June 2023). 19. Definitions of key concepts from the WHO patient safety curriculum guide. Geneva: World Health Organization; 2012 (https://www.who.int/publications/i/item/9789241501958, accessed 6 June 2023). Annexes 35 20. The conceptual framework for the international classification for patient safety. Geneva: World Health Organization; 2009 (https://apps.who.int/iris/bitstream/handle/10665/70882/WHO_IER_PSP_2010.2_eng.pdf, accessed 6 June 2023). 21. Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017;17:230. https://doi.org/10.1186/s12877-017-0621-2. 22. Chang CB, Chen JH, Wen CJ, Kuo HK, Lu IS, Chiu LS et al. Potentially inappropriate medications in geriatric outpatients with polypharmacy: application of six sets of published explicit criteria. Br J Clin Pharmacol. 2011;72(3):482–9. https://doi.org/10.1111/j.1365-2125.2011.04010.x, https://www.ncbi.nlm.nih.gov/ pubmed/21557760. 23. Medication safety in transitions of care: Technical report. Geneva: World Health Organization; 2019 (https://apps. who.int/iris/handle/10665/325453, accessed 6 June 2023). 36 Medication without harm: policy brief Annex 2: Pledge to support implementation of the third WHO Global Patient Safety Challenge: Medication Without Harm Unsafe medication practices and medication errors are a leading cause of injury and avoidable harm in health care systems across the world. WHO launched the third WHO Global Patient Safety Challenge: Medication Without Harm to focus on strengthening systems to improve medication safety by reducing medication errors and avoidable medication-related harm. The goal is reducing the rate of severe, avoidable harm related to medicines globally. More information is available at https://www.who.int/initiatives/medication-without-harm I, _________________ [INSERT NAME TITLE/DESIGNATION], on behalf of _____________________________ [ORGANIZATION and COUNTRY], _____________________________________________________________ hereby pledge to support implementation of the WHO Global Patient Safety Challenge, to protect patients from medication-related harm and make health care safer, through: 1. developing a plan on how our organization can support WHO Global Patient Safety Challenge: Medication Without Harm, after assessment of our current work; 2. identifying ways to support and implement an action plan on the three flagship areas: high-risk situations, polypharmacy and transitions of care; 3. engaging with key stakeholders at national and global levels to prioritize medication safety; 4. promoting active participation of patients and families through education and engagement for safe medication use; 5. raising awareness of the public and/or the health workforce on medication safety through campaigns and education; 6. supporting a culture of safety that encourages transparency, non-punitive action and learning from errors; and 7. sharing best practices and progress with WHO and key stakeholders. ________________________________________ _____________________________ [SIGNATURE] [DATE AND PLACE] E-mail address: ___________________________ Patient Safety Flagship Unit Integrated Health Services Department World Health Organization 20, Avenue Appia 1211 Geneva 27 Switzerland Email: patientsafety@who.int Website: https://www.who.int/health-topics/patient-safety