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GLASS Methodology for surveillance of national antimicrobial consumption

Global Antimicrobial Resistance and Use Surveillance System (GLASS)

GLASS Methodology for surveillance of national antimicrobial consumption

Global Antimicrobial Resistance and Use Surveillance System (GLASS) GLASS methodology for surveillance of national antimicrobial consumption ISBN 978-92-4-001263-9 (electronic version) ISBN 978-92-4-001264-6 (print version) © World Health Organization 2020 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. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization (http://www.wipo.int/amc/en/mediation/rules/). Suggested citation. GLASS methodology for surveillance of national antimicrobial consumption. Geneva: World Health Organization; 2020. Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data. CIP data are available at http://apps.who.int/iris. Sales, rights and licensing. To purchase WHO publications, see http://apps.who.int/bookorders. To submit requests for commercial use and queries on rights and licensing, see http://www.who.int/about/licensing. Third-party materials. If you wish to reuse material from this work that is attributed to a third party, such as tables, figures or images, it is your responsibility to determine whether permission is needed for that reuse and to obtain permission from the copyright holder. The risk of claims resulting from infringement of any third- party-owned component in the work rests solely with the user. General disclaimers. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of WHO concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement. 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. Design and layout by 400 Communications Limited. Contents

Abbreviations v 4.3.2. National reporting 18 4.4. Reporting metrics 18 1 Introduction 2 4.5. Contextual information relating to data collection 18 2 The GLASS component on surveillance of national antimicrobial consumption 4 5 Data management 20 2.1. Global Antimicrobial Resistance and Use 5.1. Data flow between countries and WHO 20 Surveillance System (GLASS) 4 5.2. Data collection 20 2.2. Aim and objectives of GLASS-AMC 4 5.2.1. Collection of AMC data 20 2.2.1. Aim 4 5.2.2. WHO template for data collection 21 2.2.2. Objectives 5 5.3. Data submission 21 2.3. Three-level structure of surveillance of 5.4. Data analysis 22 national AMC 5 5.5. Dissemination of data 22 2.3.1. National level 5 2.3.2. Regional level 5 6 GLASS-AMC IT platform 24 2.3.3. Global level 5 6.1. Users 24 2.4 Setting up a national surveillance system 6.2. Data submission 24 for AMC 6 6.2.1. Data upload 24 6.3. AMC data questionnaire 25 3 Methodology 8 3.1. Definitions 8 Annexes 27 3.2. Measurement issues 8 Annex 1 Introduction to ATC and 3.3. The ATC/DDD system 8 DDD methodology 28 3.3.1. The ATC classification 8 Annex 2 List of ATC subgroups 3.3.2. Unit of measurement (DDD) 9 under surveillance 35 3.4. Antimicrobials 9 Annex 3 Definition of variables for 3.5. Health care sectors and levels 10 AMC surveillance 37 3.5.1. The community health care level 10 Annex 4 AMC data questionnaire 45 3.5.2. The hospital health care level 10 Annex 5 Specification of the GLASS-AMC 3.5.3. Public and private health care sectors 10 product level data file 48 3.6. Data sources for consumption estimates 11 Annex 6 Specification of the GLASS-AMC Substance Level Data file 53 3.6.1. Flow of antimicrobials 11 Annex 7 Measurement unit list 55 3.6.2. Potential sources of information on AMC 11 Annex 8 Administration route list 55 Annex 9 Salt list 55 4 Data collection for AMC 16 Annex 10 List of DDD for combined products 56 4.1. Elements of data collection 16 Annex 11 Product origin list 60 4.2. AMC data 16 Annex 12 Conversion factor list 60 4.2.1. Product level data 17 Annex 13 Health care sector list 60 4.2.2. Substance level data 17 Annex 14 Health care level list 60 4.3. Denominator data 17 4.3.1. Global reporting 17

iii Abbreviations

AMC antimicrobial consumption GLASS Global Antimicrobial Resistance and Use Surveillance System AMR antimicrobial resistance INN international nonproprietary name ATC Anatomical Therapeutic Chemical classification system NGO nongovernmental organization CC collaborating centre NFP national focal point DDD Defined Daily Dose OIE World Organisation for Animal Health DID Defined Daily Doses/1000 inhabitants/ OTC over-the-counter day PBIRG Pharmaceutical Business Intelligence EphMRA European Pharmaceutical Market and Research Group Research Association PDD prescribed daily dose FAO Food and Agriculture Organization PIY packages/1000 inhabitants/year GAP-AMR Global Action Plan on antimicrobial UN United Nations resistance WHO World Health Organization

iv SECTION 01 GLASS Methodology for surveillance of national antimicrobial consumption

1. Introduction

At the Sixty-eighth World Health Assembly held in May • monitor the outcomes of interventions aimed at 2015, Member States adopted the Global Action Plan changing the use of antimicrobials; on antimicrobial resistance (GAP-AMR). The World • assess the quality of prescribing against practice Health Assembly urged Member States to implement guidelines; the action plan, recognizing that this may need to be adapted to specific contexts and national priorities. • raise awareness in health professionals, consumers and policy-makers about the The GAP-AMR has five objectives: contribution of inappropriate use of antimicrobials 1. Improve awareness and understanding of in human health to the emergence and spread of antimicrobial resistance. antimicrobial resistance. 2. Strengthen surveillance and research. In 2016, in response to the lack of data on antimicrobial consumption (AMC) in many Member States, especially 3. Reduce the incidence of . in low- and middle-income countries, WHO initiated the 4. Optimize the use of antimicrobial medicines. surveillance of AMC for the collection, analysis and 5. Ensure sustainable investment in countering reporting of data on AMC in human health. This included antimicrobial resistance. two main components: development of standardized surveillance tools, and support to countries in In Objective 2, surveillance and monitoring are establishing corresponding national surveillance acknowledged as critical components of the response systems. After developing the methodological tools, to AMR. In 2015, the World Health Organization (WHO) WHO rolled out its first cycle of data collection to launched the Global Antimicrobial Resistance and Use gather consumption data for the 2014–2016 period in Surveillance System (GLASS) to: an initial set of countries enrolled in the programme. • improve understanding of the spread and drivers of This first phase included supporting implementation AMR, including the use of antimicrobial medicines; of national surveillance systems in certain low- and middle-income countries. As a result of this pilot phase • standardize surveillance based on officially of data collection, WHO published its first global report recognized data across countries; and and presented data on antimicrobial consumption from 1 • inform effective control strategies to tackle AMR. 65 countries and areas around the world. Specifically related to GAP-AMR Objective 4, Member In 2020, following the pilot phase, the surveillance of States are requested to provide “stewardship AMC became mainstream within GLASS, allowing programmes that monitor and promote optimization Member States to report their national AMC data to of antimicrobial use at national and local levels in WHO in a systematic manner. This reporting provides accordance with international standards in order to a unique opportunity to access data on both AMC and ensure the correct choice of medicine at the right dose AMR in a central repository, facilitating the coordinated on the basis of evidence”. global fight against AMR. Thus, an important element of the GAP-AMR is The Tripartite organizations - WHO, FAO and OIE - have monitoring the use of antimicrobials, both in terms of developed a joint monitoring and evaluation framework 2 strengthening the surveillance and optimizing the use for the GAP-AMR. Using this framework, countries can of antimicrobials. follow their progress on implementation of national programmes for surveillance of AMC. In addition, the Data on the use of antimicrobials can be used, for framework defines specific indicators related to the use example, to: of antimicrobials under Outcome 4: Optimized use of • relate exposure to antimicrobials to the antimicrobials in human and animal health, with some development of antimicrobial resistance; of these indicators being based on data generated by national surveillance programmes on AMC. • identify and provide early warning of issues relating to changes in exposure and use of antimicrobials, and develop interventions to address identified problematic areas;

1 See https://apps.who.int/iris/bitstream/handle/10665/277359/9789241514880-eng.pdf?ua=1 2 See https://www.who.int/antimicrobial-resistance/global-action-plan/monitoring-evaluation/tripartite-framework/en/

2 The GLASS component on surveillance of national antimicrobial consumption

SECTION

3 GLASS Methodology for surveillance of national antimicrobial consumption

2. The GLASS component on surveillance of national antimicrobial consumption

2.1.Global Antimicrobial Resistance Escherichia coli across human, environment and animal sectors (the “Tricycle”) and point prevalence and Use Surveillance System (GLASS) studies on antimicrobial use in humans. In alignment with the work on the GAP-AMR, 2.2. Aim and objectives of GLASS-AMC GLASS promotes integration with other surveillance programmes in public health, and in the animal, 2.2.1. Aim agriculture, and environment sectors. GLASS evolves continuously; for example three types AMR-related The aim of the GLASS component on surveillance of surveillance activities have been developed and added national AMC (GLASS-AMC) is to provide a common to the system. The various types of AMR-related and standardized methodology for measuring and surveillance activities led by GLASS are grouped into reporting the consumption of antimicrobial agents at technical modules. (Fig. 2.1). country level. This standardization allows the monitoring of trends over time, facilitates comparisons between A major step forward in 2020 was the addition of global countries, and provides a common metric for reporting surveillance of AMC to be reported on an annual basis. antimicrobial use at regional and global levels. In addition, focused surveillance and survey approaches have been developed, some of which are already starting The surveillance of AMC is a key to inform strategies to be implemented. Focused surveillance activities to optimize the use of antimicrobials. AMC data can include the emerging AMR reporting component (the indicate the availability and affordability of antimicrobial GLASS-EAR), the special project on AMR in Neisseria agents, and in conjunction with other data, such as gonorrhoeae (Enhanced Gonococcal Antimicrobial AMR data, inform the development of clinical guidelines Surveillance Programme [EGASP]), and surveillance of and protocols, as well as restrictions on use of agents AMR in bloodstream caused by Candida spp. for particular clinical conditions or to nominated Studies that have been successfully applied in several prescribers. These steps, which are necessary to ensure countries include the “One Health” AMR surveillance optimal use of antimicrobials, are beyond the scope of model assessing the occurrence of ESBL-producing this document.

Fig. 2.1. GLASS activities

ROUTINE DATA SURVEILLANCE FOCUSSED SURVEILLANCE SURVEYS AND STUDIES

Enhanced Gonorrhoeae Emerging Antimicrobial surveillance (GLASS-EGASP) Antimicrobial Resistance Resistance Reporting surveillance (GLASS-AMR) (GLASS-EAR) One Health AMR surveillance (GLASS-One Health)

Point Prevalence Survey methodology for AMU in hospital Candida spp. Antimicrobial Consumption AMR surveillance surveillance (GLASS-AMC) (GLASS-Fungi) GLASS methodology for estimating attributable mortality of AMR bloodstream infections

4 The GLASS component on surveillance of national antimicrobial consumption

2.2.2. Objectives The team should also facilitate linkages with AMC surveillance across human health, animal health and The specific objectives of the surveillance of national environmental sectors in the country. To operate and AMC are to provide: have support from the national authorities, the AMC • a methodology that can be integrated in the team should be placed under the authority of the package of tools to assist the national strategy on ministry of health, or other national health authority optimising the use of antimicrobials (e.g. national mandated by the ministry of health (e.g. national action plans on AMR); regulatory authority). • information on quantities and types of consumed All Member States are invited to participate in the antimicrobials for policy-makers and prescribers; global surveillance and share their national AMC data with WHO at the GLASS platform (GLASS-AMC). • a common methodology to the countries for Participation involves formal enrolment in GLASS- collecting, analysing and reporting national AMC, establishment of a national coordinating team or antimicrobial consumption data; group and nomination of a GLASS-AMC national focal • reliable and comparable national consumption point for communication with WHO GLASS. data over time and between countries; 2.3.2. Regional level • a methodology for collecting global antimicrobial consumption data as part of GLASS; At regional level, WHO is responsible for supporting countries in implementing their national surveillance • comparable consumption data with animal and system on AMC and for coordinating the WHO agricultural consumption data. surveillance programme. In terms of support, WHO regional offices assist countries in their capacity- 2.3. Three-level structure of building efforts for AMC surveillance at national level. surveillance of national AMC In terms of coordination, the regional offices ensure that information and expertise on AMC in the region The surveillance of AMC involves actors at three levels is shared among the countries, and that countries – national, regional and global – as outlined below. report their national data to WHO. WHO analyses consumption data, provides regular reports on AMC in 2.3.1. National level the regions, and supports country efforts for optimal Countries are responsible for collecting, analysing and use of antimicrobials. Also, the GLASS-AMC platform reporting on AMC at national level on a routine basis, facilitates coordination between countries and their and should use this information on AMC to take actions respective WHO Regional Offices. to improve the use of antimicrobials. For this, countries 2.3.3. Global level would need to set up a national surveillance system to monitor antimicrobial consumption at national At global level, WHO is responsible for providing level as part of their AMR national action plans and its standardized methodologies, tools and technical implementation. expertise (in coordination and consultation with the other Countries should also develop a strategy for AMC levels), and for coordinating global surveillance of AMC surveillance at national level, that defines the objectives in line with regional specificities. At global level, WHO of the surveillance, and designates an AMC national also collates national consumption data submitted by team or group that is responsible for establishing and the countries into GLASS-AMC, analyses these data and managing the AMC surveillance system. The national provides regular global reports on AMC; WHO makes team is thus responsible for identifying data sources, these data available to the other levels for further analysis collecting and validating the consumption data with and production of reports. the data providers, sharing the information at country level for further policy actions and finally reporting the consumption data to WHO via the GLASS platform.

5 GLASS Methodology for surveillance of national antimicrobial consumption

2.4. Setting up a national • If applicable, meet with the data providers to inform them about the purpose of the surveillance surveillance system for AMC programme and how the requested data will be used. If necessary, organize a workshop with the data The tasks required to set up a national system for providers to train them on how to report. surveillance of antimicrobial consumption can be grouped into six main steps, as outlined below. • Agree with the data providers on the data submission process and legal considerations related to data Step 1: Structures and governance ownership, sharing and dissemination. • Identify the government agency, unit or participants Step 4: Data collection and validation who will lead the national programme under the supervision of the national authorities. • Set up tools for data collection, starting with simple tools. • Establish a multidisciplinary AMC national team with clear terms of reference, and ensure that the team has, • Initiate data collection. as a minimum, the core set of skills in pharmaceutical • Work with data providers to validate data. supply chain systems and data management needed to run the surveillance system. Step 5: Data analyses • Establish a technical working group on surveillance of • Develop a data analysis plan that outlines the results AMC to support the AMC national team; the working to be generated according to objectives and target group should be linked to, or be part of, the national audience. AMR committee. • Clean and analyse the data according to the data • Identify the different actors involved in the surveillance analysis plan. activities and their roles. • Report and publish results on AMC to inform national • Appoint a national focal point to liaise with WHO. strategies to optimize antimicrobial use and to To ensure good integration of the surveillance of AMC combat AMR. with other national activities related to antimicrobial • Submit national data to the WHO through the GLASS use and AMR, it is important that the AMC national platform on an annual basis. team collaborates with other AMR programmes (e.g. for surveillance of AMR as part of the “One Health” approach, Step 6: Sustainability and long-term and for surveillance of antimicrobial use and AMR in the plans animal and agricultural sectors). • Develop IT tools for data collection. Consider Where there are multiple data providers, including from setting up electronic support systems to facilitate the private sector, it may be necessary to put contracts in data extraction. Automate data collection as much place or develop legal tools to ease the release of data by as possible to reduce manual work; automation these providers. decreases the risk of data errors and promotes sustainability. Consider how representative the data Step 2: Objectives and methodology are, and whether the data quality and coverage can • Define the objectives and outputs of the national be improved. If it is not possible to obtain complete programme on AMC. coverage initially, simply start small, validate data quality and scale up over time. • Become familiar with the WHO methodology on AMC monitoring, including the Anatomical • Consider how to ensure sustainability of the AMC Therapeutic Chemical/Defined Daily Dose (ATC/ surveillance programme (e.g. funding, capacity- DDD) classification system. building and structures). Step 3: Data sources • Consider how to collaborate with other relevant surveillance programmes (e.g. AMR, and AMC in the • Identify possible data sources for monitoring AMC agriculture sector). and select the most suitable data sources, given the objectives and resources available.

6 Methodology

SECTION

7 GLASS Methodology for surveillance of national antimicrobial consumption

3. Methodology

3.1. Definitions Measuring consumption data is an important starting point for countries with limited experience in data For the purpose of the protocol presented, the following collection. With experience and as data sources definitions apply: become more sophisticated (e.g. e-prescribing records), it is expected that there will be more emphasis refer to • Antimicrobial consumption (AMC) data on measuring antimicrobial use. estimates derived from aggregated data sources such as import or wholesaler data, or aggregated 3.2. Measurement issues health insurance data, which provide no information available on the patients who receive the medicines There is a need for a common system of classification or why the antimicrobials are being used. These and standard metrics to facilitate comparisons of data sources provide a proxy estimate of use of AMC between health facilities, between countries antimicrobials. and between regions. The most commonly used Consumption data may be presented as total classification system is the ATC classification system. consumption for a country or may be disaggregated The most commonly used measurement metric is the by health care setting (community or hospital, and number of DDDs. These are discussed in more detail in public or private sectors). the following section and in Annex A. • Antimicrobial use data refer to estimates derived 3.3. The ATC/DDD system from patient-level data. These data may allow disaggregation based on patient characteristics 3.3.1. The ATC classification (e.g. gender and age), or indication for which the medicine is being used. Depending on the source The ATC classification system is the most commonly of information, it may be possible to determine used method for aggregation of medicines data, and the patients’ symptoms, physician diagnoses it allows flexibility in reporting by medicine or groups and ordered. This will facilitate of medicines. In this system, the active substances are assessment of clinical practice against agreed divided into different groups according to the organ protocols and treatment guidelines. or system on which they act, and their therapeutic, pharmacological and chemical properties.

Table 3.1. Definitions of the ATC levels

LEVEL 1 Level 1 indicates the anatomical main group and consists of one letter. There are 14 main groups. The group most relevant to work on antimicrobials is group J Antiinfectives for systemic use. However, some antimicrobials are classified in other main groups; for example, used as intestinal antiinfectives are in ATC main group A Alimentary tract and , while some oral and rectal anti-protozoal agents are in ATC main group P products, insectides and repellants. LEVEL 2 Level 2 indicates pharmacological and therapeutic subgroups; for example, J01 is Antibacterials for systemic use, J02 Antimycotics and J04 . LEVEL 3 Level 3 indicates chemical or pharmacological subgroups; for example, J01C is Beta-lactam antibacterials, . LEVEL 4 Level 4 indicates the pharmacological subgroup; for example, J01CA is Penicillins with extended spectrum. LEVEL 5 Level 5 indicates the chemical substance; for example, J01CA01 is and J01CA04 is . ATC: Anatomical Therapeutic Chemical.

8 Methodology

Medicines are classified in groups at five different levels, 3.4. Antimicrobials as shown in Table 3.1. More information on the ATC system is provided in The WHO surveillance focuses only on antimicrobials for Annex A, and the full list of assigned ATC codes is systemic use; topical antimicrobials are excluded. available online.3 WHO has defined a core set of antimicrobials that all 3.3.2. Unit of measurement (DDD) countries should include in their surveillance programme, as shown below: The most commonly used measurement statistic is the number of DDDs. The DDD is the assumed average ANTIBACTERIALS J01 maintenance dose per day for a medicine used for its main indication in adults. A DDD is only assigned for drugs ANTIBIOTICS FOR ALIMENTARY TRACT A07AA that already have an ATC code. The DDD, however, is only DERIVATIVES FOR P01AB a technical unit of use; it does not necessarily reflect the PROTOZOAL DISEASES recommended or average prescribed dose. The DDDs for the antiinfectives are generally based on use in infections of moderate severity. However, some In addition, the WHO surveillance programme includes an antiinfectives are only used in severe infections and their optional list of antimicrobials that countries may include DDDs are assigned accordingly. in their surveillance programme according to local needs and resources, as shown below: There are no separate DDDs for children, which makes the DDD estimates for paediatric formulations more difficult J02 to interpret. The number of DDDs is calculated as follows: ANTIMYCOTICS D01BA

Total grams used ANTIVIRALS J05 Number of DDDs = DDD value in grams ANTIMYCOBACTERIALS FOR J04A Where the total amount of the medicine used (in grams) is TREATMENT OF determined by summing the amounts of active ingredient ANTIMALARIALS P01B across the various formulations (e.g. different strengths of tablets or capsules, syrup formulations or injections) and pack sizes. Finally, countries may include in their national surveillance The number of DDDs provides a measure of extent of programme extra antimicrobial agents that are not in the use; however, for comparative purposes these data are core or optional lists. In such cases, countries should usually adjusted for population size or population group, collect and report the results of these additional analyses depending on the medicines of interest and the level of separately at national level. data disaggregation that is possible. Countries should liaise with their Regional AMC team For most antimicrobials, the DDDs/1000 inhabitants/day regarding reporting of any additional analyses at regional (DID) will be calculated for the total population, including level. For example, there may be interest in reporting all age and gender groups. consumption of tuberculosis (TB) medicines in regions where there are several countries with large populations It may also be possible to stratify the national estimates by of patients requiring treatment. age group, gender and health care sectors (community and hospital, public and private). Where there is stratification A list of medicines and ATC codes is provided in Annex B. there needs to be careful consideration of the appropriate estimate for the denominator (e.g. DDDs/1000 children <5 years/day or DDDs/1000 women/day).

3 See http://www.whocc.no/atc_ddd_index/

9 GLASS Methodology for surveillance of national antimicrobial consumption

3.5. Health care sectors and levels emergency departments – antimicrobials dispensed by the hospitals for outpatient care should be included in The surveillance methodology considers two health care the community health care level. It might not be possible sectors (public and private) and two health care levels to split inpatient and outpatient AMC in the databases (hospital and community). of the data providers, and this often results in outpatient consumption being wrongly reported as hospital It is possible to collect data for both sectors or for only consumption. In such cases, this limitation should be one sector if data for the other sector are not available. noted as a deviation from the standard methodology, When collecting data for both sectors, it is possible to because it can influence the overall consumption figures collect the data separately (i.e. public and private) or as a and impede comparisons with other countries. whole (i.e. global sector). In a similar way, data can be collected for both levels or for 3.5.2. The hospital health care level only one level if data for the second level are not available. The hospital sector corresponds to care provided to Again, data can be disaggregated (i.e. community and inpatients (admitted patients) in health care facilities. hospital) or not (i.e. total level). These can include general and district hospitals, as The combination of reporting health care sectors and well as secondary and tertiary care hospitals and other levels is summarized in Table 3.2. specialist health clinics. The ability to collect disaggregated data depends on the In many countries, antimicrobials reported in the hospital capacity and experience of data providers to capture sector are usually prescribed by hospital doctors and the consumption data and on the types and structure of administered to the patients directly by the health the surveillance databases. As the national surveillance professionals in those facilities. In other countries, systems mature over time, countries are gradually moving antimicrobials for inpatients might be purchased from from aggregated to disaggregated data collection. community pharmacies, and this can result in hospital consumption being wrongly reported as community 3.5.1. The community health care level consumption. If this scenario occurs frequently, leading to an overestimate of the consumption of some hospital The community health care level corresponds to primary medicines at the community level, this should be noted care and may also include outpatient hospital care; it is when reporting consumption data. sometimes referred to as ambulatory care. Primary care is care provided, for example, by general practitioners 3.5.3. Public and private health care (GPs), family doctors, nurses, physician assistants, sectors pharmacists, dentists and clinical officers. Residential care (e.g. nursing homes, day care centres) is also Disaggregation of AMC data for the public and private typically considered to belong to the community sector. health care sectors is facilitated by the fact that the actors, flow and channels of medicines are often clearly In many countries, antimicrobials reported in the differentiated between the two health care sectors. community sector are usually prescribed by GPs, community nurses or health workers. Antimicrobials are It may be more difficult to collect data from the private dispensed or supplied to the patients in pharmacies or health care sector. In that case, regulations or laws may licensed drug stores. In other countries, people are more need to be altered to make reporting of data on AMC likely to seek primary care from hospital outpatient or mandatory for private actors.

Table 3.2. Combinations of health care sectors and levels

LEVEL / SECTOR PUBLIC PRIVATE GLOBAL

Community Hospital Total

10 Methodology

3.6. Data sources for consumption a prescription. Borders may be “porous”, with illegal imports and exports. Patients may buy products in estimates neighbouring countries where products are cheaper or more available. Thus, the flow of antimicrobials can be 3.6.1. Flow of antimicrobials complex and initial mapping is required to identify the Procurement and supply of antimicrobial agents at relevant data sources for national AMC data. the country level may be complex. In its simplest 3.6.2. Potential sources of information on and “idealized” form, for a country without domestic manufacturing capacity, antimicrobials are first imported AMC (as licensed imports with customs records); then Information on the AMC can be obtained from five levels supplied and distributed by licensed wholesalers and of the value chain of medicines as shown in Fig. 3.1. The distributors to public and private hospitals, community levels are: health facilities and community pharmacies; and finally • procurement and supply dispensed to patients based on prescriptions written by appropriately registered health care professionals. • distribution In some countries, these medicines will be reimbursed • prescribing by health insurance programmes, with or without the imposition of patient co-payments. • dispensing The reality in many countries (with manufacturing • patient use. capacity) is quite different. Antimicrobials may There are several potential sources of information on be sourced from both international and domestic AMC at each level: producers. Imports may be subject to re-export to other countries, and domestic producers may export part of • procurement and supply level their production. Orders may be placed with wholesalers – import data (using data from customs records or directly with manufacturers. Imported products may and declaration forms) be used in the veterinary and agriculture sectors as well as for human use. Health care professionals and patients – production records of domestic manufacturers may be able to import products directly. Antimicrobials (excluding any exports of products) may be purchased over-the-counter as well as with

Fig. 3.1. Value chain of medicines

Post-market surveillance Use Pharmaco- vigilance Substandard Dispensing and falsified Pharmacies medicines Prescribing Insurances of medicines Hospitals Distribution Primary health acare Wholesalers Hospitals Procurement Central and supply medical stores Selection Imports Doctors Manufacturers Regulation Marketing authorization Research and Import development Manufacturers

11 GLASS Methodology for surveillance of national antimicrobial consumption

• distribution level authorized importation, a complex array of local and multinational manufacturers, multiple wholesalers in the – wholesaler and distributor data – this could be public and private sectors, an insurance authority that data on procurement by wholesalers, or records covers only some sectors of the population, and private of sales by the wholesalers to health care health care providers (e.g. hospitals, clinics and health facilities and pharmacies care professionals) that may be reluctant to provide – public sector procurement records – these exist information. where there is both centralized and decentralized It will be up to governments in Member States to decide purchasing of medicines for the public sector whether data collection is voluntary or mandatory across – donations or programmes – this may relate to all providers and all sectors. Changes in regulation or laws particular international health programmes (e.g. might be necessary to oblige the data providers to deliver for HIV, TB or malaria), or for special populations the requested information. such as migrants and refugees where medicines Data sources that are close to the patient will provide would be provided by nongovernmental the most reliable estimates of AMC, and will be more organizations (NGOs) likely to provide data on age and gender of the patient, • dispensing level provider details and indication for the antimicrobial – records from community and hospital prescription. However, these sources will also be the most pharmacies, and licensed drug stores sophisticated and most expensive. – data from health insurance programmes The WHO methodology allows for flexibility in the choice of data sources, ranging from import and production • prescribing level records to patient data, enabling countries with limited – prescribing records of doctors and dispensing resources to use pre-existing data sources to build records of pharmacists sustainable programmes for the surveillance of AMC. – patient use level It is important to correctly identify the data sources that are used to collect AMC data in the country and, if more – information on antimicrobial use from patients than one data source is used, to be aware of the overlaps themselves. in the information provided. If the sources are treated These sources provide information with differing levels of as separate estimates and summed to provide “total detail on the consumption and use of antimicrobials. It is consumption”, this may overestimate actual AMC. important to understand the nature, scope and limitations According to the WHO methodology, data are collected of the data collection from each of these sources, to avoid from official channels without capturing antimicrobials under- or over-estimation of AMC. Table 3.3. summarizes sold on the informal (illegal) market. For countries with some of the strengths and of each of these a significant informal market, other types of monitoring data sources. (e.g. surveys) may be more suitable for capturing these The sources also differ in terms of difficulty of gathering data. Each country should at least try to estimate or information. For example, there may be a single import approximate the share held by the informal market in authority in the public sector that retains records of all order to interpret AMC data.

12 Methodology

Table 3.3. Strengths and limitations of data sources for AMC

DATA SOURCE STRENGTHS LIMITATIONS

Import data • Import permits issued by government • Documentation may be incomplete • Centralized records • May include parallel trade stock • Standardized reporting for customs movements declaration forms, including product • May not account for smuggled goods type (generic or branded), volume, port or illegal entry of products of origin, country of manufacture, batch • Volumes match import cycles rather number and expiry date than consumption patterns • Includes OTC medicines • Are administrative records and thus are not formatted for research and analysis Domestic • Local licensed producers should be • Private companies may be unwilling to manufacturers easily identified provide data • Can separate product volumes for local • Volumes reflect production rather than use and for export consumption patterns • Can request data in format suitable for analysis Public sector • Likely to have reasonable • Only provides data for public sector procurement documentation of purchases • May not reflect total public sector • Possible to disaggregate distribution consumption if other procurement is data to facility types (community and undertaken by hospitals and health hospital) and geographical location facilities • May be single (or limited number) of • May include stock procured but never procurement agencies supplied Wholesalers • Only legal entity able to import • In some countries, medical, dental, medicines for distribution veterinary practitioners and • Can provide purchase and supply data pharmacists can also import medicines • Supply data may be disaggregated (e.g. • May be difficult to get data from private by community or hospital, regions or sector facility type) • Many wholesalers in some settings • Data collection easier where numbers • May supply other smaller wholesalers of wholesalers are limited not “end users” • Distribution and supply data are likely • Wholesalers may provide agriculture to be closer to actual consumption than and veterinary sectors as well as for purchase data human use Donations and • May represent a significant proportion • May be difficult to differentiate programmes of antimicrobials dispensed for specific donations for local population and clinical programmes or specific special populations (e.g. migrants and populations refugees)

13 GLASS Methodology for surveillance of national antimicrobial consumption

DATA SOURCE STRENGTHS LIMITATIONS

Community and hospital • Sales from pharmacies or drug • Large number of facilities makes data pharmacies, drug stores stores are closer to the actual use of collection resource intensive dispensing data antimicrobials by the patients • May be difficult to collect data where • Can separate community and hospital only manual records exist sectors • May be difficult to get information from • Potentially can separate public and private sector private sectors • Does not take into account compliance • May include some OTC medicines with therapy Health insurance data • Patient-level consumption data • May be difficult to get information from • May be disaggregated by patient private sector demographic characteristics • Only reimbursed antimicrobials • Geographical data may be available reported • Possible to disaggregate to community • Selected populations covered by health and hospital sectors insurance, may not be representative of • Often limited number of data providers whole population • Data more accessible if public sector • Administrative records may not include agencies all the variables of interest Prescribing records of • May have patient characteristics, • Prescribed medicines may not be (health professionals or diagnosis, dose, duration, co-prescribed dispensed databases) medicines • Samples of prescribers may not be representative and therefore may not reflect national data Community, household • Patient-level data will be available • Time-consuming and labour-intensive survey data • Most closely reflects actual to collect the data consumption • Issues of representativeness of the • Repeat surveys can provide longitudinal data collected data Commercial data • Standardized data collection • Data must be purchased sources (e.g. IQVIA – • Capacity to combine data from multiple • Data collection may be limited in some previously IMS Health) sources, including manufacturer countries records, hospital and pharmacy data • May not be able to examine data at regional, local, facility or prescriber level • EphMRA/PBIRG classification is used rather than ATC codes, so information at the pharmacological or chemical subgroup level may be limited AMC: antimicrobial consumption; ATC: Anatomical Therapeutic Chemical; EphMRA: European Pharmaceutical Market Research Association; OTC: over the counter; PBIRG: Pharmaceutical Business Intelligence and Research Group.

14 Data collection for AMC

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15 GLASS Methodology for surveillance of national antimicrobial consumption

4. Data collection for AMC

AMC is defined as quantities of antimicrobials used by 4.1. Elements of data collection a population in a specific setting (e.g. community or hospital health care levels) during a specific period of There are three elements to the data collection: AMC time (e.g. days, months and year). data, denominator data, and descriptive or contextual For global reporting, national estimates of consumption information that is relevant for interpreting the are reported for the calendar year (i.e. January to consumption estimates calculated (see Fig. 4.1). December). 4.2. AMC data For national reporting, and for better understanding of the dynamics of the consumption of antimicrobials, it is WHO accepts two different types of AMC data: advised to collect and report data: • product level data • on a quarterly or monthly basis – to take into • substance level data account seasonal variations often linked with different disease patterns; or Product level data are the standard, default data expected by WHO. However, where product level data • at subnational level – to take into account are not available, countries could submit substance level geographical variability and socioeconomic data. The two types of AMC data are discussed below. determinants of the use of antimicrobials. In terms of methodology, the ATC/DDD classification system standardizes the data collection, calculation and reporting of AMC.

Fig. 4.1. Elements of data collection

• Product level data

Antimicrobial • Consumed packages at product level (aggregated packages) consumption data • May be stratified by health care levels and sectors

• Population under surveillance to which data apply Denominator data • May be stratified by health care sectors

• Data source information; for example, national reference data (total) or health care Contextual sector (community or hospital) information related • Which antimicrobials are included in surveillance to antimicrobial consumption • Specific exclusions of health care institutions (e.g. nursing homes, day care centres, psychiatric facilities and private sector)

16 Data collection for AMC

4.2.1. Product level data The product content and the DDD must be expressed in the same units. Register Number of DDDPi = The first step requires identification of all the products Product content x Number of consumed packages for the antimicrobial agents registered (i.e. with Pi Pi marketing authorization) in the country; that is, a DDDPi valid and complete national register of products. The register corresponds to the list of all antimicrobial Finally, the consumption of DDD for each product is medicinal products covered by the surveillance system. aggregated to be reported by the ATC substance code. It contains detailed information about the medicinal products, divided into three areas: identifying the 4.2.2. Substance level data product, calculating consumption and breaking down consumption into more fine-grained details for further At substance level, consumption is expressed in terms analyses. The set of standard variables for the register of the ATC substance. For each ATC substance, the is described in Annex C. consumption expressed in DDD is obtained by dividing the total quantities of active substances by the DDD of The register is used to link each medicinal product with the corresponding ATC. its corresponding ATC substance code. Depending on the capacities of the national pharmaceutical system The total consumed quantities and the DDD must be of the country, the link with the ATC substance code expressed in the same units. may or may not have already been made during the Number of DDDATCi = authorization or registration procedure. In the case of Total consumed quantities registration, the link with the code will need to be done ATCi specifically for the national surveillance programme. DDDATCi Owing to the authorization or withdrawal of new products and the annual updates of the ATC/DDD Where the total consumed quantities of the medicines system, it is mandatory to update the register file at are determined by summing the amounts of active least once a year in order to integrate these changes. ingredient across the various formulations (e.g. different strengths of tablets or capsules, or syrup Package data formulations) and pack sizes. Consumption is expressed as the total number of packages for each product listed in the register that 4.3. Denominator data are consumed by the population in the defined setting during the defined period of time. The total numbers of DDDs derived as consumption estimates should be adjusted for the population to In some countries, the consumed products may be which the data apply. counted not by package but by item (e.g. as number of tablets or number of vials). In such cases, the product 4.3.1. Global reporting package size should be set to 1 and the reported number For global reporting, WHO use United Nations (UN) of packages will actually be the number of items. population statistics as standardized population Consumption data estimates for all Member States. The consumption expressed in DDD is calculated by When the surveillance system does not include the multiplying the content of active substances in each whole population, countries can provide – as part of the product by the number of packages of that product, and AMC data questionnaire (Annex D) – the percentage of dividing it by the corresponding DDD. total population covered by the surveillance system.

17 GLASS Methodology for surveillance of national antimicrobial consumption

WHO will correct the UN population according to the When data are provided at product level, if the package figures provided by countries, and will then report size of each product is known, it is possible to estimate consumption per population. consumption in number of units (e.g. tablets, vials or bottles of syrup). However, when data are provided at 4.3.2. National reporting substance level, such estimation is not possible. Countries should use the best estimates of the population covered by the surveillance system. This 4.5. Contextual information relating is important when the surveillance system includes to data collection specific populations not normally counted in national statistics (e.g. refugees). It is important to report the sources of data used, the health care levels and sectors involved, the antimicrobial 4.4. Reporting metrics agents included in the surveillance, and whether any specific groups of patients or facility types have been The standard reporting metric used by WHO for national excluded from the calculations (e.g. nursing homes, estimates is DDD/1000 inhabitants/day (DID). day care centres, psychiatric facilities or rehabilitation Another relevant metric for national estimates is DDD/ units). inhabitant/day. When countries report to WHO, they should fill in the Using these metrics, it is possible to estimate the AMC data questionnaire (Annex D), which includes this average number of people treated on a day or the type of information. average number of days of treatment per person in one Using the contextual information will facilitate the year period, based on the assumption that one DDD validation and proper reporting by WHO of the data equals one day of treatment. This measure needs to be shared by countries. interpreted carefully.

18 Data management

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19 GLASS Methodology for surveillance of national antimicrobial consumption

5. Data management

5.1. Data flow between countries and At national level, the data collection process can be WHO split into different tasks as suggested below: 1. For the initial data collection, the national team Within the framework of a global WHO programme on develops protocols and trains the data providers to surveillance of AMC, countries submit data to WHO report AMC to the team. through the GLASS IT platform. The three levels of WHO (country, regional and global) interact with countries 2. Every year, the national team sends a call for AMC through the GLASS IT platform for data submission, data to the data providers. validation, analysis and finally for reporting (Fig.5.1). 3. The data providers deliver the requested information to the national team in the agreed 5.2. Data collection format. 5.2.1. Collection of AMC data 4. The national team checks and validates the data delivered by the data provider. If there are issues Collection of data on AMC, population and contextual with the data or if clarifications are needed, the information (collected through the questionnaire) is national team contacts the data providers. the responsibility of the country and its surveillance programme’s AMC national team. At country level, 5. Once the data have been validated, the national protocols, forms and related documents provided by team prepares the data for submission to WHO. WHO might be translated into national language. If The interaction with WHO can be initiated before necessary, extra documents such as training materials the data are validated, to smooth the process may be produced by countries to facilitate the national of data submission and validation between the data collection. To ensure a reliable data collection country and WHO. process, the national data providers may need training 6. The national team analyses and reports the data on which data to collect and how to report those data to at national level. Some countries may prefer to the AMC national team. submit data to WHO at this step. The data collection is annual and involves different 7. The national team analyses the data collection stakeholders; the collection is coordinated by the process and results, and makes changes to the national AMC team (Fig. 5.2). protocol for the next annual data collection.

Fig. 5.1. Flow of data between countries and WHO

WHO global level

WHO regional WHO country GLASS level level

Data flow Country Data validation WHO coordination

20 Data management

Fig. 5.2. Annual data collection

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5.2.2. WHO template for data collection – the list of products Aims of template – the consumed number of packages per year, and the health care sectors and levels. WHO has developed an Excel file, the AMC Excel Using the AMC Excel template, countries can export template, to help national AMC teams to manage their data that matches the GLASS-AMC specifications, into country’s data.4 Countries can use this file to enter their a file that can be submitted to the GLASS IT platform. register of antimicrobial medicines; enter consumption per year, per health care sector and per level; produce A manual for AMC data management4 includes a simple consumption figures; and generate the data file detailed description of the template, and explains for submission into GLASS-AMC. how to use it and how to produce simple descriptive statistics on AMC. The Excel template includes some macros that automatically validate the data or make calculations. 5.3. Data submission Nevertheless, countries should check their data to assess their relevance before sharing the results Data submission involves the country and WHO. produced by the Excel template. Data submission is done through the GLASS IT platform and its GLASS-AMC module (which are only accessible Structure of template to the registered national AMC teams and to WHO The WHO AMC Excel template has multiple worksheets staff). Each country only has access to its own data. for entering: The data submission process is separated into the • data for the main ATC groups and health care following steps: sectors and levels per year 1. The AMC national team submits nationally • population per year validated consumption data, population data and questionnaire responses in the GLASS-AMC • consumption data at product level including: module.

4 See https://www.who.int/activities/facilitating-global-surveillance-of-antimicrobial-resistance

21 GLASS Methodology for surveillance of national antimicrobial consumption

2. The AMC national team validates and approves the down the consumption by groups of interests submitted data in the GLASS-AMC module. (e.g. using the AWaRe [Access, Watch, Reserve] classification, by period of time or settings or 3. WHO checks the approved data for coherence. population if available); and 4. WHO publishes the data. • identify changes over time or between settings, and WHO may identify errors in data submitted by countries formulate a hypothesis to explain the difference or may request clarifications before approving the data. that could be discussed with relevant experts. These may require national AMC teams to contact data Where analysis of the consumption data identifies providers to obtain the correct figures or additional inappropriate use of these medicines, it should lead to information (Fig. 5.3). further action. WHO will only publish data that has been approved by It is important that countries develop their own capacity countries. At any time, if there are errors, countries can to undertake the analyses of AMC data, by training request withdrawal of data that have been previously the staff in charge of surveillance but also by using approved and published, and can re-submit data with resources in the academic sector. WHO should provide the correct figures. technical support to countries to ensure these data are The validation of data by WHO should be done at the WHO used in a proper manner at country level. WHO will also regional level with the support of the WHO global level. provide analyses and reports at regional and global level, for global policy-makers. 5.4. Data analysis Analysis of the consumption data is a key step in the 5.5. Dissemination of data surveillance programme. The analysis serves to: Although there is Member State agreement for reporting • generate metrics or indicators of AMC that will be of AMC estimates to WHO for regional and global understandable by relevant health professionals reporting, the data are useful primarily at country level. and stakeholders – mainly through calculating Countries should share findings with all stakeholders consumption by classes of antimicrobials through various communication channels; for example, (expressed in DDD per population) but also breaking through national reports, public websites, scientific publications and dissemination workshops.

Fig. 5.3. GLASS submission and validation processes

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22 GLASS-AMC IT platform

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23 GLASS Methodology for surveillance of national antimicrobial consumption

6. GLASS-AMC IT platform

The GLASS IT platform5 for global surveillance on AMR, 6.2. Data submission AMC and AMU, launched by WHO in 2016, is a common environment for sharing data between Member States The GLASS-AMC provides various functions for and WHO. The platform hosts IT elements for GLASS countries submitting their data: technical components. • upload of data file; The GLASS-AMC IT platform allows: • validation and revocation of submitted data; • countries to submit and validate their national AMC • download of submitted data and consumption data to WHO; metrics; and • the three levels of WHO to access data submitted • access to auto-generated analysis reports. by countries; 6.2.1. Data upload • countries to produce their national AMC reports; and The GLASS-AMC platform allows countries to upload data as: • WHO to generate a global database on AMC. • product level data, or The GLASS-AMC platform accepts consumption data from countries in two formats: product level data and • substance level data. substance level data. Both formats are expected to be uploaded as tabbed The platform calculates consumption metrics (as DDD) files. Depending on the language, users should specify using the latest version of the ATC/DDD that is available the format of the decimal character used in the data file in the platform, and reports consumption per population (i.e. either dot or comma). using the UN population figures and coverage figures When new data are uploaded, the GLASS-AMC platform provided by countries. calculates consumption metrics at substance level. When a new ATC/DDD index is added into the platform, Product level data it recalculates all consumption metrics accordingly. By default, GLASS-AMC accepts the product level data, 6.1. Users as defined in Annex E. Using this format, countries When a country enrols with GLASS-AMC, the have information on consumption, but also important nominated national focal point (NFP) is registered as information on the antimicrobial products and market such in the GLASS-AMC IT platform. If alternates have shaping, which allows additional analysis. WHO will not been nominated, they will be also registered into the publish any consumption data that includes product platform. In addition, the NFP has viewer access to the names. Compared with substance level data, the other GLASS components. product level format allows better validation of the data by countries and WHO. When a previously nominated NFP is no longer active, the country needs to inform WHO so that the NFP’s access can be removed.

5 See https://extranet.who.int/glass/portal/

24 GLASS-AMC IT platform

Substance level data questionnaire per year). The questionnaire addresses five areas: When a country cannot report product level data, they can report substance level data, as defined in Annex • ATC classes reported; F. In contrast to product level data, reporting data at • data sources used (e.g. importation, central drug substance level will not allow additional information on store and pharmacies); market shaping and has limited validation options. • proportion of the population covered by the data; 6.3. AMC data questionnaire • level of care (community versus hospital) and On the GLASS IT platform, the AMC national team health care sectors (public versus private) covered submits the AMC data questionnaire responses, in by the data; and addition to the validated consumption data. • shortage of antimicrobials. Responses to the questionnaire provide general The AMC national team can share a different set of information on the uploaded data and should accompany information for each ATC class (see Annex D for details). each new submission of consumption data (one

25

Annexes

ANNEXES

27 GLASS Methodology for surveillance of national antimicrobial consumption

Annex 1 Introduction to ATC and DDD methodology

Categorization of medicines a recommendation for use, nor does it imply any judgements about efficacy or relative efficacy of The Anatomical Therapeutic Chemical (ATC) drugs and groups of drugs. classification system is the most commonly used method for aggregation of medicines data; it allows The first level of the code indicates the anatomical flexibility in reporting by medicine or groups of main group and comprises one letter. There are 14 medicines. The classification of a substance in main groups as shown here: the ATC/Defined Daily Dose (DDD) system is not

ATC main groups

A Alimentary tract and metabolism B Blood and blood forming organs C Cardiovascular D Dermatologicals G Genito-urinary system and sex hormones H Systemic hormonal preparations, excluding sex hormones and insulin J Antiinfectives for systemic use L Antineoplastic and immunomodulating agents M Musculo-skeletal system N Nervous system P Anti-parasitic products, insecticides and repellants R Respiratory system S Sensory organs V Various

28 Annexes

The structure and nomenclature used in the ATC Medicinal products containing two or more active classification system is illustrated for metformin (used ingredients are considered as combinations in the ATC in the treatment of diabetes) in Box A1. system and have a different ATC code to the single components. There are a number of challenges with the use of the ATC system. In some cases, a medicine can be used In addition, there are regular revisions of the ATC code for different indications, and this is not always reflected to deal with new drugs and changes in use of products. in the ATC code. In some cases, medicines will have When interpreting trends over time, it is important to be several different ATC codes depending on the use of aware of changes in ATC codes that may have occurred the product (e.g. for systemic use or topical use). over time.

Box A1. The ATC classification system In the ATC classification system, active substances are divided into different groups according to the organ or system on which they act, and their therapeutic, pharmacological and chemical properties. Drugs are classified in groups at five different levels. The drugs are divided into 14 main groups (1st level), with pharmacological/therapeutic subgroups (2nd level). The 3rd and 4th levels are chemical/pharmacological/ therapeutic subgroups, and the 5th level is the chemical substance. The 2nd, 3rd and 4th levels are often used to identify pharmacological subgroups when that is considered more appropriate than therapeutic or chemical subgroups. The complete classification of metformin is shown here to illustrate the structure of the code: A Alimentary tract and metabolism (1st level, anatomical main group) A10 Drugs used in diabetes (2nd level, therapeutic subgroup) A10B Blood glucose lowering drugs, excl insulins (3rd level, pharmacological subgroup) A10BA (4th level, chemical subgroup) A10BA02 Metformin (5th level, chemical substance) Thus, in the ATC system, all plain metformin preparations are given the code A10BA02. Nomenclature International nonproprietary names (INN) are preferred. If an INN name has not been assigned, a United States Adopted Name (USAN) or British Approved Name (BAN) is usually chosen.

The WHO Collaborating Centre for Drug Statistics Methodology has developed coding rules for all medicines. In relation to antimicrobials, the 2016 guidelines6 state the following:

J01 ANTIBACTERIALS FOR SYSTEMIC USE This group comprises antibacterials for systemic use, except antimycobacterials, which are classified in J04. The antibacterials are classified according to their mode of action and chemistry. Combinations of two or more systemic antibacterials from different third levels are classified in J01R, except combinations of sulfonamides and , which are classified at a separate 4th level, J01EE. Combinations of antibacterials with other drugs, including local anesthetics or vitamins, are classified at separate 5th levels in the respective antibacterial group by using the 50-series. Common cold preparations containing minimal amounts of antibacterials are classified in R05X. Inhaled antiinfectives are classified here based on the fact that preparations for inhalation cannot be separated from preparations for injection.

6 See https://www.whocc.no/atc_ddd_index/?code=J01

29 GLASS Methodology for surveillance of national antimicrobial consumption

Application of the ATC classification Level 5 (chemical substance): system J01CA PENICILLINS WITH EXTENDED SPECTRUM

The antiinfective agents for systemic use are classified ATC CODE NAME under ATC main group J (level 1). J01CA01 ampicillin Level 1 (Main group): ATC main group J (Antiinfective for systemic use) J01CA02 J01CA03 Level 2 (pharmacological/therapeutic subgroups): J01CA04 amoxicillin J ANTIINFECTIVES FOR SYSTEMIC USE J01CA05 J01 Antibacterials for systemic use J01CA06 J02 Antimycotics for systemic use J01CA07 J04 Antimycobacterials J01CA08 J05 Antivirals for systemic use J01CA09 J06 Immune sera and immunoglobulins J01CA10 J07 Vaccines J01CA11 Level 3 (chemical/pharmacological/therapeutic J01CA12 subgroups): J01CA13 J01 ANTIBACTERIALS FOR SYSTEMIC USE J01CA14 J01A J01CA15 J01CA16 J01B J01CA17 J01C Beta-lactam antibacterials, penicillins J01CA18 J01D Other beta-lactam antibacterials J01CA19 aspoxicillin J01E Sulfonamides and trimethoprim J01CA20 combinations J01F , and J01CA51 ampicillin, combinations J01G antibacterials J01M Quinolone antibacterials J01R Combinations of antibacterials J01X Other antibacterials Level 4 (chemical/pharmacological/therapeutic subgroups): J01C BETA-LACTAM ANTIBACTERIALS, PENICILLINS J01CA Penicillins with extended spectrum J01CE Beta-lactamase sensitive penicillins J01CF Beta-lactamase resistant penicillins J01CG Beta-lactamase inhibitors J01CR Combinations of penicillins, J01CR Combinations of penicillins, incl. beta-lactamase inhibitors

30 Annexes

Some examples of ATC codes Changes of ATC codes and new codes 1. Amoxicillin is J01CA04 and is classified as follows: ATC codes can change over time as more experience is gained with the medicine and more products become J ANTIINFECTIVES FOR SYSTEMIC USE available. The WHO ATC/DDD website7 provides (Level 1) information on alterations to ATC codes between 2005 and J01 ANTIBACTERIALS FOR SYSTEMIC USE 2020. New ATC codes can also be found on the website.8 (Level 2) Antimicrobials with multiple ATC J01C BETA-LACTAM ANTIBACTERIALS, PENICILLINS (Level 3) codes J01CA Penicillins with extended spectrum Some antimicrobials are classified under more than (Level 4) one ATC code (e.g. and ), reflecting their use in different clinical situations. J01CA04 Amoxicillin (Level 5) Metronidazole Note: J01CA04 applies to amoxicillin in all its formulations (e.g. oral, parenteral and syrup formulations for children). A01AB17 Alimentary tract and metabolism, Antiinfectives and for local oral 2. is J01DD04 and is classified as follows: treatment J ANTIINFECTIVES FOR SYSTEMIC USE D06BX01 Dermatologicals, Other chemotherapeutics (Level 1) G01AF01 Genitourinary system and sex hormones, J01 ANTIBACTERIALS FOR SYSTEMIC USE derivatives (Level 2) J01XD01 Antiinfectives for systemic use, Imidazole J01D OTHER BETA-LACTAM derivatives ANTIBACTERIALS (Level 3) P01AB01 Antiparasitic products, insecticides and J01DD Third-generation repellants, Nitroimidazole derivatives (Level 4) P01AB51 Antiparasitic products, insecticides and J01DD04 Ceftriaxone (Level 5) repellants, Nitroimidazole derivatives, 3. Amoxicillin + is J01CR02 and is metronidazole combinations classified as follows: Vancomycin J ANTIINFECTIVES FOR SYSTEMIC USE A07AA09 Alimentary tract and metabolism, (Level 1) Intestinal antiinfectives J01 ANTIBACTERIALS FOR SYSTEMIC USE J01XA01 Antiinfectives for systemic use, (Level 2) Other antibacterials, Glycopepeptide J01C BETA-LACTAM ANTIBACTERIALS, antibacterials PENICILLINS (Level 3) To determine the total use of each of these J01CR Combinations of penicillins including antimicrobials, it will be necessary to include all the beta-lactamase inhibitors (Level 4) relevant ATC codes. However, for metronidazole, the WHO methodology indicates that only J01XD01 and J01CR02 Amoxicillin and inhibitor P01AB01 are to be used, because the other codes refer (Level 5) to metronidazole for local or topical use.

7 See http://www.whocc.no/atc_ddd_alterations__cumulative/atc_alterations/ 8 See http://www.whocc.no/atc/lists_of_new_atc_ddds_and_altera/new_atc/

31 GLASS Methodology for surveillance of national antimicrobial consumption

Defined Daily Dose (DDD) Example of calculation of DDD for The most commonly used measure for reporting of antimicrobial agent drug utilization is number of DDDs, where the DDD is the assumed average maintenance dose per day for Substance M: 1000 mg on the first day, then 500 a drug used for its main indication in adults. A DDD mg daily. Duration of therapy: 14 days is only assigned for drugs that already have an ATC DDD is 500 mg (maintenance dose as total code. Converting aggregate quantities to DDDs allows duration of the treatment course is more than a rough estimation of the potential treatment days for 1 week) which the pharmaceutical is procured or consumed. The DDD, however, is only a technical unit of use; it does Substance M: 1000 mg on the first day, then 500 not necessarily reflect the recommended or average mg daily. Duration of therapy: 5 days prescribed dose. DDD is 600 mg ((1000 + 4x500)/5 = 600 mg) The DDDs for the antiinfectives are generally based on use in infections of moderate severity. However, some antiinfectives are only used in severe infections, and The DDD is a technical unit of measurement, and it does their DDDs are assigned accordingly. not necessarily reflect the doses that are prescribed Generally, DDDs assigned are based on daily treatment. and used in practice. The prescribed daily dose (PDD) However, in the case of antimicrobial agents, there is the average daily dose prescribed; it is obtained from are rules to guide calculation of the DDD based on the a representative sample of prescriptions. duration of the treatment. The DDD remains a useful metric because it is a For antiinfectives given in a high initially starting dose standardized measure and can be applied to all data. followed by a lower daily “maintenance” dose, the When interpreting the results of the analysis, it is DDDs are based on the “maintenance” dose if the total important to think about possible differences with duration of the treatment course is more than 1 week. prescribed daily doses. However, if the treatment course is 7 days or less, the DDDs are assigned according to the average daily dose (i.e. the total course dose divided by the number of treatment days).

32 Annexes

Returning J01CA Penicillins with extended spectrum, the assigned DDD values are as shown here:

ATC CODE NAME DDD UNIT OF DDD ADMINISTRATION ROUTE J01CA01 ampicillin 2 g O 6 g P 2 g R J01CA02 pivampicillin 1.05 g O J01CA03 carbenicillin 12 g P J01CA04 amoxicillin 3 g P 1,5 g O J01CA05 carindacillin 4 g O J01CA06 bacampicillin 1.2 g O J01CA07 epicillin 2 g O 2 g P J01CA08 pivmecillinam 0.6 g O J01CA09 azlocillin 12 g P J01CA10 mezlocillin 6 g P J01CA11 mecillinam 1.2 g P J01CA12 piperacillin 14 g P J01CA13 ticarcillin 15 g P J01CA14 metampicillin 1.5 g O 1.5 g P J01CA15 talampicillin 2 g O J01CA16 sulbenicillin 15 g P J01CA17 temocillin 2 g P J01CA18 hetacillin 2 g O J01CA19 aspoxicillin 4 g P J01CA20 combinations J01CA251 ampicillin, combinations DDD: defined daily dose; g: gram; O: oral; P: parenteral.

Note: There are three DDD values for ampicillin, and two each for amoxicillin, epicillin and metampicillin. For epicillin and metampicillin, the DDDs remain the same for oral and parenteral administration, but this is not the case for all antimicrobials.

33 GLASS Methodology for surveillance of national antimicrobial consumption

Some examples of where the DDD changes according to the formulation are shown here:

ATC CODE NAME DDD UNIT OF DDD ADMINISTRATION ROUTE J01CR02 amoxicillin and 1.5 g O 3 g P J01FA01 1 g O erthyromycin ethylsuccinate 2 g O 1 g P J01MA02 1 g O 0.5 g P J01GB01 0.112 g Inhal. powder 0.3 g Inhal. Solution 0.24 g P P01AB01 metronidazole 2 g O P01AB01 metronidazole 2 g R J01XD01 metronidazole 1.5 g P DDD: defined daily dose; g: gram; inhal: inhalation; O: oral; P: parenteral; R: rectal.

Notes: template according to whether the product is for oral, parenteral, inhalation or rectal administration. 1. The DDD for amoxicillin and enzyme inhibitor is the same as the DDD for amoxicillin alone. The DDD 4. In the case of metronidazole, J01 only includes for the combination is based on the main active the forms for parenteral administration. For total ingredient. use of metronidazole, it will be necessary to use all the relevant ATC codes for systemic use. Data for 2. Erythromycin ethylsuccinate has a special code P01AB01 are included in the AMC template. for salt (ESUC) in the data collection template to ensure that the correct DDD is applied. If there is no ATC code available or there is no DDD assigned for product, contact the GLASS-AMC team at 3. The different DDD values for ciprofloxacin, [email protected] for advice. tobramycin and metronidazole are assigned in the

34 Annexes

Annex 2 List of ATC subgroups under surveillance

CODE NAME CORE SET A07AA Antibiotics Mandatory D01BA Antifungals for systemic use Optional J01AA Tetracyclines Mandatory J01BA Amphenicols Mandatory J01CA Penicillins with extended spectrum Mandatory J01CE Beta-lactamase sensitive penicillins Mandatory J01CF Beta-lactamase resistant penicillins Mandatory J01CG Beta-lactamase inhibitors Mandatory J01CR Combinations of penicillins, incl. beta-lactamase inhibitors Mandatory J01DB First-generation cephalosporins Mandatory J01DC Second-generation cephalosporins Mandatory J01DD Third-generation cephalosporins Mandatory J01DE Fourth-generation cephalosporins Mandatory J01DF Mandatory J01DH Mandatory J01DI Other cephalosporins and Mandatory J01EA Trimethoprim and derivatives Mandatory J01EB Short-acting sulfonamides Mandatory J01EC Intermediate-acting sulfonamides Mandatory J01ED Long-acting sulfonamides Mandatory J01EE Combinations of sulfonamides and trimethoprim, incl. derivatives Mandatory J01FA Macrolides Mandatory J01FF Lincosamides Mandatory J01FG Streptogramins Mandatory J01GA Mandatory J01GB Other Mandatory J01MA Fluoroquinolones Mandatory J01MB Other quinolones Mandatory J01RA Combinations of antibacterials Mandatory J01XA Glycopeptide antibacterials Mandatory J01XB Mandatory J01XC antibacterials Mandatory J01XD Imidazole derivatives Mandatory J01XE derivatives Mandatory J01XX Other antibacterials Mandatory

35 GLASS Methodology for surveillance of national antimicrobial consumption

CODE NAME CORE SET J02AA Antibiotics Optional J02AB Imidazole derivatives Optional J02AC derivatives Optional J02AX Other antimycotics for systemic use Optional J04AA Aminosalicylic acid and derivatives Optional J04AB Antibiotics Optional J04AC Optional J04AD Thiocarbamide derivatives Optional J04AK Other drugs for treatment of tuberculosis Optional J04AM Combinations of drugs for treatment of tuberculosis Optional J04BA Drugs for treatment of lepra Optional J05AA Thiosemicarbazones Optional J05AB Nucleosides and excl. inhibitors Optional J05AC Cyclic amines Optional J05AD Phosphonic acid derivatives Optional J05AE Protease inhibitors Optional J05AF Nucleoside and reverse transcriptase inhibitors Optional J05AG Non-nucleoside reverse transcriptase inhibitors Optional J05AH Neuraminidase inhibitors Optional J05AR Antivirals for treatment of HIV infections, combinations Optional J05AX Other antivirals Optional P01AB Nitroimidazole derivatives Optional P01BA Aminoquinolines Optional P01BB Biguanides Optional P01BC Methanolquinolines Optional P01BD Diaminopyrimidines Optional P01BE and derivatives, plain Optional P01BF Artemisinin and derivatives, combinations Optional P01BX Other antimalarials Optional N04BB derivatives Optional

36 Annexes

Annex 3 Definition of variables for AMC surveillance

The variables for AMC surveillance are split into three groups of data: • product information • consumption information • population information The tables show the variables for each of these three groups.

Variables for ‘Product information’

VARIABLE COUNTRY Description Three-letter code uniquely identifying the reporting country. Data type Coded value Variable type Mandatory Information List of country codes based on the ISO3166 alpha-3 country codes list (ref: https://en.wikipedia.org/wiki/ISO_3166-1_alpha-3)

VARIABLE PRODUCT_ID Description The national code of the medicinal product. The code that uniquely identifies the medicinal product for the country. Data type Text Variable type Mandatory Information In theory, it is important that the Product_ID should not change over time. When a product is no longer available on the market or is no longer registered, its Product_ID should not be attributed to another product; this makes it possible to identify the old product for historical purposes (prescription history). In practice, when no formal code exists for a product, the country should provide one arbitrary code that should uniquely identify the product for a specific year.

VARIABLE LABEL Description The label of the medicinal product. If possible, the label should contain the name of the medicinal product, package size, strength and pharmaceutical form. Data type Text Variable type Mandatory Information The label is an important variable because it is the only information that allows an external reviewer to cross check the medicinal product package.

37 GLASS Methodology for surveillance of national antimicrobial consumption

VARIABLE PACKSIZE Description The package size of the medicinal product. The size of the product should be reported as the number of pieces in the package, except for syrup where it should be reported as the number of mL. Data type Number Variable type Mandatory Information For products that are administrated as liquid form (i.e. syrup), the package size should be reported as mL of final reconstituted product. For all other pharmaceutical forms, the package size must be reported as the number of pieces. For instance, for vials, the package size must be reported as a number of vials in the package and not as the volume of reconstituted product. VARIABLE PACKSIZE_UNIT Description The unit of the package size of the medicinal product. Data type Coded value Variable type Mandatory Information The measurement unit in which the package size of the medicines is expressed. See Measurement unit list (Annex G) for coded values. VARIABLE ROUTE_ADMIN Description The route of administration of the medicinal product. Data type Coded value Variable type Mandatory Information The route of administration is used to attribute a DDD to the product and to report consumption according to the route of administration. See Administration route list (Annex H) for coded values. VARIABLE STRENGTH Description The strength of the active substance of each item, as defined by PACKSIZE. For multi- ingredient products, this field should contain the strength in which the DDD is expressed. Data type Number Variable type Mandatory Information For some specific substances used in combination with others, the WHO Collaborating Centre (CC) has defined some rules; for example, to only take into account the antimicrobial substance and not the combined substance (e.g. amoxicillin/clavulanic acid). For products with multiple antimicrobial substances, the WHO CC has defined DDD for combined products. In such cases, the strength should be reported in the same unit as the DDD for the corresponding combined product.

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VARIABLE STRENGTH_UNIT Description The unit of the strength of the medicinal product. Data type Coded value Variable type Mandatory Information The measurement unit in which the strength of the product is expressed. See Measurement unit list (Annex G) for the coded values. VARIABLE INBASQ Description The basic ingredient quantity (INBASQ) used for describing concentration of fluids (e.g. 200 mg/10 mL) such as syrups. In syrups and solutions, INBASQ describes the denominator part of the strength. In all other cases (including perfusion fluids or ampullas), the INBASQ should be set to 1. Data type Number Variable type Mandatory Information The default value is 1 when the package size is not expressed in mL VARIABLE INBASQ_UNIT Description The unit of the INBASQ of the medicinal product. Data type Coded value Variable type Mandatory Information The measurement unit in which the basic ingredient quantity of the product is expressed. See Measurement unit list (Annex G) for the coded values. VARIABLE ATC5 Description The WHO ATC code at substance level (ATC 5th level) of the medicinal product Data type Coded value Variable type Mandatory Information Each ATC code is linked to its product main therapeutic use. The ATC5 variable is used to attribute a DDD to the medicinal product package (MPP) and to report antimicrobial consumption according to the ATC classification. See ATC classification (Annex A). VARIABLE SALT Description The code of the salt associated to the active substance. Data type Coded value Variable type Optional Information It is only valid for methenamin (J01XX05) and erythromycin (J01FA01); for all other substances, the salt should not be specified. This is because the WHO CC has defined DDD depending on the salt for only these two substances. See the Salt list (Annex I) for the coded values.

39 GLASS Methodology for surveillance of national antimicrobial consumption

VARIABLE COMBINATION Description The code of the combined product of the medicinal product Data type Coded value Variable type Optional Information If the product is a combined product with a corresponding entry in the combined product list, the variable must be set in order to attribute the correct DDD to the product. In addition, if the variable is set, the strength unit should be reported in Unit Doses. See the combined product list (Annex J) for the coded values. VARIABLE PAEDIATRIC_PRODUCT Description The product is a paediatric medicinal product. Data type YES/NO Variable type Optional Information The product is a paediatric product or not. VARIABLE FORM Description The pharmaceutical form of the medicinal product. Data type Text Variable type Optional Information VARIABLE PRODUCT_NAME Description The name of the medicinal product. Data type Text Variable type Optional Information The name of the product. The name should be common to all products with different formulation of the same product. VARIABLE INGREDIENTS Description The name of the ingredients in the medicinal product. Data type Text Variable type Optional Information INN names should be used to report the ingredients. Any other non-active substances should be reported in addition to the antimicrobial substances. VARIABLE PRODUCT_ORIGIN Description The source of the product. Data type Coded value Variable type Optional Information The source of the product can be import, donation or locally produced. See the Product origin list (Annex K) for the coded values.

40 Annexes

VARIABLE MANUFACTURER_COUNTRY Description Three-letter code uniquely identifying the country of manufacturing. Data type Coded value Variable type Optional Information See COUNTRY variable VARIABLE MARKET_AUTH_HOLDER Description The name or code of marketing authorization holder. Data type Text Variable type Optional Information VARIABLE GENERICS Description The medicinal product is a generic. Data type YES/NO Variable type Optional Information VARIABLE YEAR_AUTHORIZATION Description Year of marketing authorization granted Data type Number Variable type Optional Information The year should be reported as a four-digit number YYYY VARIABLE YEAR_WITHDRAWAL Description Year of marketing authorization withdrawn Data type Number Variable type Optional Information The year should be reported as a four-digit number YYYY VARIABLE CONV_FACTOR Description The conversion factor to transform strength expressed in international units (IU) into strength expressed in grams (G). Data type Number Variable type Mandatory Information If there is no need to convert from IU to G, the CONV_FACTOR must be set to 1. If strength is expressed in IU and DDD in G, and no conversion factor exists, no DDD per MPP will be calculated and no consumption for this MPP will be reported. See the Conversion factor list (Annex L).

41 GLASS Methodology for surveillance of national antimicrobial consumption

VARIABLE PACKCONTENT Description The content of active substance in the medicinal product. Data type Number Variable type Mandatory Information The package content of the product is calculated by multiplying the package size by the strength, dividing by the INBASQ and multiplying by the CONV_FACTOR. VARIABLE PACKCONTENT_UNIT Description The unit of the package content of the medicinal product. Data type Coded value Variable type Mandatory Information The measurement unit in which the package content of the product is expressed. See Measurement unit list (Annex G) for coded values. VARIABLE WHO_DDD Description The official WHO DDD of the medicinal product. Data type Number Variable type Mandatory Information The WHO DDD is assigned according to the ATC5, ROUTE_ADMIN, COMBINATION and SALT variables. Some products will not have a corresponding WHO DDD, either because no ATC5 code has been assigned for the product or because no DDD has been defined for the ATC5. In the latter case, no DDD will be calculated and no consumption for this product will be reported. VARIABLE WHO_DDD_UNIT Description The unit of the WHO DDD of the medicinal product. Data type Coded value Variable type Mandatory Information The measurement unit in which the WHO DDD of the product is expressed. See Measurement unit list (Annex G) for coded values. VARIABLE DPP Description The number of calculated DDD in the package for the medicinal product. Data type Number Variable type Mandatory Information The number of DPP is calculated by dividing the PACK_CONTENT by the WHO_DDD.

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Variables for the ‘Consumption information’

VARIABLE COUNTRY Description Three-letter code uniquely identifying the reporting country. Data type Coded value Variable type Mandatory Information List of country codes based on the ISO3166 alpha-3 country codes list (ref: https://en.wikipedia.org/wiki/ISO_3166-1_alpha-3)

VARIABLE YEAR Description The year of the reported consumption data Data type Number as YYYY Variable type Mandatory Information The year of the reported consumption (as a four-digit number), not the year when data are reported. For instance, if 2018 data are reported into 2020, the YEAR variable should be set to 2018. VARIABLE PRODUCT_ID Description The national code of the medicinal product. The code that uniquely identifies the medicinal product for the country. Data type Text Variable type Mandatory Information See the Product information table above. VARIABLE HEALTH CARE_SECTOR Description The health care sector to which consumption data are reported. Data type Coded value Variable type Mandatory Information The health care sector (either public, private or both) aggregated as global. See the Health care sector list (Annex M) for the coded values. VARIABLE HEALTH CARE_LEVEL Description The health care level to which consumption data are reported. Data type Coded value Variable type Mandatory Information The health care level (either community, hospital or both) aggregated as total. See the Health care level list (Annex N) for the coded values. VARIABLE PACKAGES Description The number of packages of the medicinal product Data type Number Variable type Mandatory Information The number of packages of the medicinal product consumed for the specified year, health care sector and health care level.

43 GLASS Methodology for surveillance of national antimicrobial consumption

Variables for the ‘Population information’

VARIABLE COUNTRY Description Three-letter code uniquely identifying the reporting country. Data type Coded value Variable type Mandatory Information List of country codes based on the ISO3166 alpha-3 country codes list (ref: https://en.wikipedia.org/wiki/ISO_3166-1_alpha-3)

VARIABLE YEAR Description The year of the reported consumption data. Data type Number as YYYY Variable type Mandatory Information The year of the reported consumption (as a four-digit number), not the year when data are reported. For instance, if 2018 data are reported into 2020, the YEAR variable should be set to 2018. VARIABLE HEALTH CARE_SECTOR Description The health care sector to which consumption data are reported. Data type Coded value Variable type Mandatory Information The health care sector (either public, private or both) aggregated as global. See the Health care sector list (Annex M) for the coded values. VARIABLE HEALTH CARE_LEVEL Description The health care level to which consumption data are reported. Data type Coded value Variable type Mandatory Information The health care level (either community, hospital or both) aggregated as total. See the Health care level list (Annex N) for the coded values. VARIABLE POPULATION Description The population covered by the surveillance programme. Data type Number Variable type Mandatory Information The population covered by the surveillance programme for the specified year, health care sector and health care level.

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Annex 4 AMC data questionnaire

The antimicrobial consumption (AMC) data questionnaire 2. ATC class information aims to provide contextual information on the submitted data. It is an online questionnaire that is part of the Sectors from where data is reported GLASS-AMC platform. Please select the sectors from where data is reported: The questionnaire should be filled per year of data submitted, irrespective of the number of times data SECTOR PUBLIC PRIVATE GLOBAL for a specific year have been submitted. However, each time data for a specific year is re-submitted, the Community relevant questionnaire should be updated if necessary Hospital

(even for retrospective correction). Total Note: The questions are given here ONLY for the use Comments on the sectors reported: of the reader. If you wish to take the questionnaire, please submit your responses ONLINE. Note: An asterisk indicates that a question is mandatory to answer. Country*:

Year *:

Population coverage using United Nations population as reference 1. Introduction Do the reported data cover the same population for all reported sectors? Which ATC classes have been reported?* Yes (Specify which ATC classes you have reported data for) No A07AA (If “Yes” to the above question) D01BA Provide the percentage (as a number between 0 and J01 100) of the population covered (all population=100) J02 % J04A (If “No” to the above question) J04B Provide the percentage (as a number between 0 and J05A 100) of the population covered (all population=100) for each sector: P01B All classes SECTOR PUBLIC PRIVATE GLOBAL

Is the same data source(s) used to report consumption Community data for all substances? Hospital

(Specify if the data source(s) and sectors (public/ Total private, community/hospital) from where consumption data was collected were the same for all reported ATC Have the related consumption data been extrapolated classes) to the whole population? Yes Yes No No

45 GLASS Methodology for surveillance of national antimicrobial consumption

Comments on the reported population coverage: Production for domestic market Nongovernmental organization International programmes Central drug store Wholesalers Insurance data Hospitals Pharmacies

Public/Private sectors market share Market research companies Have you reported data for both public and private (If “No” to the above question, please answer the next sectors? two questions) Yes If you reported data for community care in the public sector, provide the data source No Import (Skip if “No” to the above question) Have you provided data grouped together (global)? Production for domestic market Yes Nongovernmental organization No International programmes Provide the estimated percentage (as a number Central drug store between 0 and 100) of the national market share Wholesalers for antimicrobials covered by the public sector (all market=100) Insurance data % Hospitals Comments on the distribution of consumption between Pharmacies the public and private sectors: Market research companies If you reported data for hospital care in the public sector, provide the data source Import Production for domestic market Nongovernmental organization International programmes Central drug store Wholesalers Data sources Insurance data Did you use the same data source to collect public sector data? Hospitals Yes Pharmacies No Market research companies (If “Yes” to the above question) Did you use the same data source to collect private sector data? Provide the data source used to collect public sector data Yes Import No

46 Annexes

(If “Yes” to the above question) Comments on the data sources: Provide the data source used to collect private sector data Import Production for domestic market Nongovernmental organization International programmes 3. Shortages Central drug store Did you have shortage at national level of antimicrobial Wholesalers substances during the year of reporting? Insurance data Yes Hospitals No Pharmacies (If “Yes” to the above question, please answer the next Market research companies two questions) (If “No” to the above question, please answer the next Please list all substances for which at least one shortage two questions) event has occurred during the year of reporting in public sector If you reported data for community care in the public sector, provide the data source Import Production for domestic market Nongovernmental organization International programmes Central drug store Please list all substances for which at least one shortage event has occurred during the year of Wholesalers reporting in private sector Insurance data Hospitals Pharmacies Market research companies If you reported data for hospital care in the public sector, provide the data source Comments on shortage Import Production for domestic market Nongovernmental organization International programmes Central drug store Wholesalers Insurance data 4. General Hospitals Overall comments on reported data Pharmacies Market research companies

47 GLASS Methodology for surveillance of national antimicrobial consumption

Annex 5 Specification of the GLASS-AMC product level data file

The GLASS-AMC Product Level Data file contains The format of GLASS-AMC is tab separated, and it variables related to: contains the variables shown below. Users should not modify the order and names of variables because • product information modification will cause the file to be rejected by the • consumption information GLASS-AMC platform.

Variables for the ‘Product Level data’ GLASS-AMC file

VARIABLE COUNTRY Description Three-letter code uniquely identifying the reporting country. Data type Coded value Variable type Mandatory Information See Annex C VARIABLE YEAR Description The year of the reported consumption data. Data type Number as YYYY Variable type Mandatory Information See Annex C VARIABLE PRODUCT_ID Description The national code of the medicinal product. Data type Text Variable type Mandatory Information See Annex C VARIABLE LABEL Description The label of the medicinal product. Data type Text Variable type Mandatory Information See Annex C VARIABLE PACKSIZE Description The package size of the medicinal product. Data type Number Variable type Mandatory Information See Annex C VARIABLE PACKSIZE_UNIT Description The unit of the package size of the medicinal product. Data type Coded value Variable type Mandatory Information See Annex C

48 Annexes

VARIABLE ROUTE_ADMIN Description The route of administration of the medicinal product. Data type Coded value Variable type Mandatory Information See Annex C VARIABLE STRENGTH Description The strength of the active substance of each item as defined by PACKSIZE. Data type Number Variable type Mandatory Information See Annex C VARIABLE STRENGTH_UNIT Description The unit of the strength of the medicinal product. Data type Coded value Variable type Mandatory Information See Annex C VARIABLE INBASQ Description The basic ingredient quantity (INBASQ) used for describing concentration of fluids. Data type Number Variable type Mandatory Information See Annex C VARIABLE INBASQ_UNIT Description The unit of the INBASQ of the medicinal product. Data type Coded value Variable type Mandatory Information See Annex C VARIABLE ATC5 Description The WHO ATC code at substance level (ATC 5th level) of the medicinal product Data type Coded value Variable type Mandatory Information See Annex C VARIABLE SALT Description The code of the salt associated with the active substance. Data type Coded value Variable type Optional Information See Annex C VARIABLE COMBINATION Description The code of the combined product of the medicinal product Data type Coded value Variable type Optional Information See Annex C

49 GLASS Methodology for surveillance of national antimicrobial consumption

VARIABLE COMBINATION Description The code of the combined product of the medicinal product Data type Coded value Variable type Optional Information See Annex C VARIABLE PAEDIATRIC_PRODUCT Description The product is a paediatric medicinal product Data type YES/NO Variable type Optional Information See Annex C VARIABLE FORM Description The pharmaceutical form of the medicinal product. Data type Text Variable type Optional Information See Annex C VARIABLE PRODUCT_NAME Description The name of the medicinal product. Data type Text Variable type Optional Information See Annex C VARIABLE INGREDIENTS Description The name of the ingredients in the medicinal product. Data type Text Variable type Optional Information See Annex C VARIABLE PRODUCT_ORIGIN Description The source of the product. Data type Coded value Variable type Optional Information See Annex C VARIABLE MANUFACTURER_COUNTRY Description Three-letter code uniquely identifying the country of manufacturing. Data type Coded value Variable type Optional Information See Annex C VARIABLE MARKET_AUTH_HOLDER Description The name or code of marketing authorization holder. Data type Text Variable type Optional Information See Annex C

50 Annexes

VARIABLE GENERICS Description The medicinal product is a generic. Data type YES/NO Variable type Optional Information See Annex C VARIABLE YEAR_AUTHORIZATION Description Year of marketing authorization granted. Data type Number Variable type Optional Information See Annex C VARIABLE YEAR_WITHDRAWAL Description Year of marketing authorization withdrawn. Data type Number Variable type Optional Information See Annex C VARIABLE GLO_TOTAL_PACKAGES Description The number of consumed packages for the global health care sector and total health care level for the specified year and product. Data type Number Variable type Optional Information If consumption data have been reported for aggregated health care sectors and levels as one figure, they should be reported in that variable. VARIABLE GLO_COMMUNITY_PACKAGES Description The number of consumed packages for the global health care sector and community health care level for the specified year and product. Data type Number Variable type Optional Information If consumption data have been reported for aggregated health care sectors and community level, they should be reported in that variable. VARIABLE GLO_HOSPITAL_PACKAGES Description The number of consumed packages for the global health care sector and hospital health care level for the specified year and product. Data type Number Variable type Optional Information If consumption data have been reported for aggregated health care sectors and community level, they should be reported in that variable. VARIABLE PUB_TOTAL_PACKAGES Description The number of consumed packages for the public health care sector and total health care level for the specified year and product. Data type Number Variable type Optional Information If consumption data have been reported for public health care sector and aggregated health care levels, they should be reported in that variable.

51 GLASS Methodology for surveillance of national antimicrobial consumption

VARIABLE PUB_COMMUNITY_PACKAGES Description The number of consumed packages for the public health care sector and community health care level for the specified year and product. Data type Number Variable type Optional Information If consumption data have been reported for public health care sector and community health care level, they should be reported in that variable. VARIABLE PUB_HOSPITAL_PACKAGES Description The number of consumed packages for the public health care sector and hospital health care level for the specified year and product. Data type Number Variable type Optional Information If consumption data have been reported for public health care sector and hospital health care level, they should be reported in that variable. VARIABLE PRIV_TOTAL_PACKAGES Description The number of consumed packages for the private health care sector and total health care level for the specified year and product. Data type Number Variable type Optional Information If consumption data have been reported for private health care sector and aggregate health care levels, they should be reported in that variable. VARIABLE PRIV_COMMUNITY_PACKAGES Description The number of consumed packages for the private health care sector and community health care level for the specified year and product. Data type Number Variable type Optional Information If consumption data have been reported for private health care sector and community health care level, they should be reported in that variable. VARIABLE PRIV_HOSPITAL_PACKAGES Description The number of consumed packages for the private health care sector and hospital health care level for the specified year and product. Data type Number Variable type Optional Information If consumption data have been reported for private health care sector and hospital health care level, they should be reported in that variable.

52 Annexes

Annex 6 Specification of the GLASS-AMC Substance Level Data file

The GLASS-AMC substance level data file contains not modify the order and names of variables because variables related to consumption information. modification will cause the file to be rejected by the GLASS-AMC platform. The format of the GLASS-AMC is tab separated, and it contains the variables shown below. Users should

Variables for the ‘Substance level data’ GLASS-AMC file

VARIABLE COUNTRY Description Three-letter code uniquely identifying the reporting country. Data type Coded value Variable type Mandatory Information See Annex C VARIABLE YEAR Description The year of the reported consumption data. Data type Number as YYYY Variable type Mandatory Information See Annex C VARIABLE ATC5 Description The WHO ATC code at substance level (ATC 5th level) of the medicinal product. Data type Coded value Variable type Mandatory Information See Annex C VARIABLE ROUTE Description The route of administration of the medicinal product. Data type Coded value Variable type Mandatory Information See Annex C VARIABLE SALT Description The code of the salt associated with the active substance. Data type Coded value Variable type Optional Information See Annex C VARIABLE SECTOR Description The code of the health care sector for which data are reported Data type Coded value Variable type Optional Information See Annex C

53 GLASS Methodology for surveillance of national antimicrobial consumption

VARIABLE TOTAL_DDD Description The number of DDD for the specified ATC5, ROUTE, SALT and SECTOR fortotal health care level. Data type Number Variable type Optional Information If consumption data expressed in DDD have been collected for the specified ATC5, ROUTE, SALT and SECTOR and for total health care level, they should be reported under this variable. VARIABLE COMMUNITY_DDD Description The number of DDD for the specified ATC5, ROUTE, SALT and SECTOR forcommunity health care level. Data type Number Variable type Optional Information If consumption data expressed in DDD have been collected for the specified ATC5, ROUTE, SALT and SECTOR and for community health care level, they should be reported under this variable. VARIABLE HOSPITAL_DDD Description The number of DDD for the specified ATC5, ROUTE, SALT and SECTOR forhospital health care level/ Data type Number Variable type Optional Information If consumption data expressed in DDD have been collected for the specified ATC5, ROUTE, SALT and SECTOR and for hospital health care level, they should be reported under this variable. VARIABLE TOTAL_TONS Description The number of metric tons for the specified ATC5, ROUTE, SALT and SECTOR fortotal health care level. Data type Number Variable type Optional Information If consumption data expressed in metric tons have been collected for the specified ATC5, ROUTE, SALT and SECTOR and for total health care level, they should be reported under this variable. VARIABLE COMMUNITY_TONS Description The number of metric tons for the specified ATC5, ROUTE, SALT and SECTOR for community health care level. Data type Number Variable type Optional Information If consumption data expressed in metric tons have been collected for the specified ATC5, ROUTE, SALT and SECTOR and for community health care level, they should be reported under this variable. VARIABLE HOSPITAL_TONS Description The number of metric tons for the specified ATC5, ROUTE, SALT and SECTOR for hospital health care level. Data type Number Variable type Optional Information If consumption data expressed in metric tons have been collected for the specified ATC5, ROUTE, SALT and SECTOR and for hospital healthcare level, they should be reported under this variable.

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Annex 7 Measurement unit list

CODE NAME MG Milligram G Gram IU International unit MU Millions of international units UD Unit dose PCS Piece ML Millilitre

Annex 8 Administration route list

CODE NAME O Oral P Parenteral R Rectal IP Inhalation powder IS Inhalation solution

Annex 9 Salt list

CODE NAME ESUC Ethylsuccinate erythromycin HIPP Hippurate methenamine MAND Mandalate methenamine

55 GLASS Methodology for surveillance of national antimicrobial consumption

Annex 10 List of DDD for combined products

The list of Defined Daily Doses (DDDs) for combined The list is updated every year according to the annual products is derived from the Anatomical Therapeutic release of the ATC/DDD system. Chemical (ATC)/DDD list of DDD for combined products. The list below is based on the 2020 version of the ATC/ Combination codes (COMB_CODE) are specific codes DDD. for the Global Antimicrobial Resistance and Use Surveillance System (GLASS) methodology.

COMB_CODE ATC5 FORM ROUTE UNIT DOSE DDD DDD_INFO (SUBSTANCES+STRENGTH) J01AA20_1 J01AA20 Tab O 115.4 mg/ 2 UD 2 UD (=2 tab) 115.4 mg/ 69.2 mg J01CA20_1 J01CA20 Tab O pivampicillin 0.25 g/ 3 UD 3 UD (=3 tab) pivmecillinam 0.2 g J01CA20_2 J01CA20 Tab O pivampicillin 0.125 g/ 6 UD 6 UD (=6 tab) pivmecillinam 0.1 g J01CE30_1 J01CE30 Powder P comb. of / 3.6 G 3.6 g expressed as for inj procaine-benzylpenicillin/ benzylpenicillin benzathine benzylpenicillin J01CR50_1 J01CR50 Tab O ampicillin 0.25 g/ 4 UD 4 UD (=4 tab) 0.25 g J01CR50_2 J01CR50 Powder P ampicillin 0.66 g/ 2 UD 2 UD (= 2 g) for inj 0.33 g J01CR50_3 J01CR50 Caps O ampicillin 0.125g/ 8 UD 8 UD (= 8 caps) oxacillin 0.125 g J01CR50_4 J01CR50 Tab O ampicillin 0.25 g/ 4 UD 4 UD (=4 tab) 0.25 g J01CR50_5 J01CR50 Powder P ampicillin 250 mg/ 2 UD 2 UD (=2 grams of for inj cloxacillin 250 mg powder for injection) J01CR50_6 J01CR50 Powder P ampicillin 500 mg/ 2 UD 2 UD (=2 grams of for inj cloxacillin 500 mg powder for injection) J01CR50_7 J01CR50 Tab O ampicillin 125 mg/ 8 UD 8 UD (=8 tab) cloxacillin 125 mg J01EC20_1 J01EC20 Tab O sulfacarbamide 0.167 g/ 4 UD 4 UD (=4 tab) 0.167 g/ 0.167 g J01EE01_1 J01EE01 Inf conc P 80 mg/ 20 20 UD (=20 ml) trimethoprim 16 mg UD J01EE01_2 J01EE01 Mixt O sulfamethoxazole 0.2 g/ 8 UD 8 UD (= 40 ml) trimethoprim 40 mg J01EE01_3 J01EE01 Tab O sulfamethoxazole 0.4 g/ 4 UD 4 UD (=4 tab) trimethoprim 80 mg J01EE02_1 J01EE02 Mixt O sulfadiazine 0.205 g/ 4 UD 4 UD (=20 ml) trimethoprim 45 mg J01EE02_2 J01EE02 Tab O sulfadiazine 0.41 g/ 2 UD 2 UD (=2 tab) trimethoprim 90 mg

56 Annexes

COMB_CODE ATC5 FORM ROUTE UNIT DOSE DDD DDD_INFO (SUBSTANCES+STRENGTH) J01EE03_1 J01EE03 Tab O 0.8 g/ 2 UD 2 UD (=2 tab) trimethoprim 0.16 g J01EE03_2 J01EE03 Powder P sulfametrole 0.8 g/ 2 UD 2 UD (defined as 2 for inj trimethoprim 0.16 g per vial vials) J01EE06_1 J01EE06 Tab O sulfadiazine 0.25 g/ 2 UD 2 UD (=2 tab) 0.1 g J01EE07_1 J01EE07 Tab O 0.12 g/ 4 UD 4 UD (=4 tab) trimethoprim 80 mg J01RA04_1 J01RA04 Tab O 1.5 MU/ 3 UD 3 UD (=3 tab) metronidazole 250 mg J01RA04_2 J01RA04 Tab O spiramycin 0.75 MU/ 6 UD 6 UD (=6 tab) metronidazole 125 mg J01RA05_1 J01RA05 Tab O 250 mg/ 2 UD 2 UD (=2 tab) 500 mg J01RA07_1 J01RA07 Tab O 1000 mg (1 tab)/ 4 UD 4 UD (=4 tab) fluconazole 150 mg (1 tab)/ 1000 mg (2 tab) (combination package) J01RA09_1 J01RA09 Tab O 200 mg/ 2 UD 2 UD (=2 tab) ornidazole 500 mg J01RA10_1 J01RA10 Tab O ciprofloxacin 500 mg/ 2 UD 2 UD (=2 tab) metronidazole 200 mg J01RA11_1 J01RA11 Tab O ciprofloxacin 500 mg/ 2 UD 2 UD (=2 tab) 600 mg J01RA11_2 J01RA11 Tab O ciprofloxacin 250 mg/ 4 UD 4 UD (=4 tab) tinidazole 300 mg J01RA12_1 J01RA12 Tab O ciprofloxacin 500 mg/ 2 UD 2 UD (=2 tab) ornidazole 500 mg J01RA13_1 J01RA13 Tab O 400 mg/ 2 UD 2 UD (=2 tab) tinidazole 600 mg J04AM02_1 J04AM02 Tab O 0.3 g/ 2 UD 2 UD (=2 tab) isoniazid 0.15 g J04AM02_2 J04AM02 Tab O rifampicin 0.15 g/ 4 UD 4 UD (=4 tab) isoniazid 0.1 g J04AM02_3 J04AM02 Tab O rifampicin 0.15 g/ 4 UD 4 UD (=4 tab) isoniazid 75 mg J04AM05_1 J04AM05 Tab O rifampicin 0.12 g/ 6 UD 6 UD (=6 tab) 0.3 g/ isoniazid 50 mg J04AM05_2 J04AM05 Tab O rifampicin 0.15 g/ 4 UD 4 UD (=4 tab) pyrazinamide 0.4 g/ isoniazid 75 mg J04AM05_3 J04AM05 Tab O rifampicin 225 mg (1 tab)/ 6 UD 6 UD (=6 tab) pyrazinamide 750 mg (1 tab)/ isoniazid 150 mg (1 tab) (combination package) J04AM05_4 J04AM05 Tab O rifampicin 60 mg/ 10 10 UD (=10 tab) pyrazinamide 150 mg/ UD isoniazid 30 mg

57 GLASS Methodology for surveillance of national antimicrobial consumption

COMB_CODE ATC5 FORM ROUTE UNIT DOSE DDD DDD_INFO (SUBSTANCES+STRENGTH) J04AM06_1 J04AM06 Tab O rifampicin 0.15 g/ 4 UD 4 UD (=4 tab) pyrazinamide 0.4 g/ 0.275 g/ isoniazid 75 mg J04AM06_2 J04AM06 Tab O rifampicin 450 mg (1 tab)/ 4 UD 4 UD (=4 tab) pyrazinamide 750 mg (2 tab)/ ethambutol 800 mg+isoniazid 300 mg (1 tab) (combination package) J04AM07_1 J04AM07 Tab O rifampicin 150 mg/ 4 UD 4 UD (=4 tab) ethambutol 275 mg/ isoniazid 75 mg J05AP51_1 J05AP51 Tab O 400 mg/ 1 UD 1 UD (=1 tab) 90 mg J05AP53_1 J05AP53 Tab O 12.5 mg/ 2 UD 2 UD (=2 tab) 75 mg/ 50 mg J05AP54_1 J05AP54 Tab O 50 mg/ 1 UD 1 UD (=1 tab) 100 mg J05AP55_1 J05AP55 Tab O sofosbuvir 400 mg/ 1 UD 1 UD (=1 tab) 100 mg J05AP56_1 J05AP56 Tab O sofosbuvir 400 mg/ 1 UD 1 UD (=1 tab) velpatasvir 100 mg/ 100 mg J05AP57_1 J05AP57 Tab O 100 mg/ 3 UD 3 UD (=3 tab) 40 mg J05AR01_1 J05AR01 Tab O 0.15 g/ 2 UD 2 UD (=2 tab) 0.3 g J05AR02_1 J05AR02 Tab O 0.6 g/ 1 UD 1 UD (=1 tab) lamivudine 0.3 g J05AR03_1 J05AR03 Tab O 0.2 g/ 1 UD 1 UD (=1 tab) 0.245 g J05AR04_1 J05AR04 Tab O zidovudine 0.3 g/ 2 UD 2 UD (=2 tab) lamivudine 0.15 g/ abacavir 0.3 g J05AR05_1 J05AR05 Tab O lamivudine 150 mg/ 2 UD 2 UD (=2 tab) 200 mg/ zidovudine 300 mg J05AR06_1 J05AR06 Tab O emtricitabine 0.2 g/ 1 UD 1 UD (=1 tab) tenofovir disoproxil 0.245 g/ 0.6 g J05AR08_1 J05AR08 Tab O emtricitabine 0.2 g/ 1 UD 1 UD (=1 tab) tenofovir disoproxil 0.245 g/ 0.025 g J05AR09_1 J05AR09 Tab O emtricitabine 200 mg/ 1 UD 1 UD (=1 tab) tenofovir disoproxil 245 mg/ 150 mg/ 150 mg J05AR11_1 J05AR11 Tab O lamivudine 300 mg/ 1 UD 1 UD (=1 tab) tenofovir disoproxil 300 mg (fumarate)/ efavirenz 600 mg

58 Annexes

COMB_CODE ATC5 FORM ROUTE UNIT DOSE DDD DDD_INFO (SUBSTANCES+STRENGTH) J05AR12_1 J05AR12 Tab O lamivudine 300 mg/ 1 UD 1 UD (=1 tab) tenofovir disoproxil 300 mg (fumarate) J05AR13_1 J05AR13 Tab O lamivudine 300 mg/ 1 UD 1 UD (=1 tab) abacavir 600 mg/ 50 mg J05AR14_1 J05AR14 Tab O 800 mg/ 1 UD 1 UD (=1 tab) cobicistat 150 J05AR15_1 J05AR15 Tab O 0.3 g/ 1 UD 1 UD (=1 tab) cobicistat 0.15 g J05AR17_1 J05AR17 Tab O emtricitabine 200 mg/ 1 UD 1 UD (=1 tab) 10 mg J05AR17_2 J05AR17 Tab O emtricitabine 200 mg/ 1 UD 1 UD (=1 tab) tenofovir alafenamide 25 mg J05AR18_1 J05AR18 Tab O emtricitabine 200 mg/ 1 UD 1 UD (=1 tab) tenofovir alafenamide 10 mg/ elvitegravir 150 mg/ cobicistat 150 mg J05AR19_1 J05AR19 Tab O emtricitabine 200 mg/ 1 UD 1 UD (=1 tab) tenofovir alafenamide 25 mg/ rilpivirine 25 mg J05AR20_1 J05AR20 Tab O emtricitabine 200 mg/ 1 UD 1 UD (=1 tab) tenofovir alafenamide 25 mg/ 50 mg J05AR21_1 J05AR21 Tab O dolutegravir 50 mg/ 1 UD 1 UD (=1 tab) rilpivirine 25 mg J05AR22_1 J05AR22 Tab O emtricitabine 200 mg/ 1 UD 1 UD (=1 tab) tenofovir alafenamide 10 mg/ darunavir 800 mg/ cobicistat 150 mg J05AR24_1 J05AR24 Tab O lamivudine 300 mg/ 1 UD 1 UD (=1 tab) tenofovir disoproxil 245 mg/ 100 mg J05AR25_1 J05AR25 Tab O lamivudine 300 mg/ 1 UD 1 UD (=1 tab) dolutegravir 50 mg P01BB51_1 P01BB51 Tab O 0.25 g/ 4 UD 4 UD (=4 tab) hydrochloride 0.1 g P01BB51_2 P01BB51 Tab O atovaquone 62.5 mg/ 16 16 UD (=16 tab) proguanil hydrochloride 25 mg UD P01BF03_1 P01BF03 Tab O 25 mg/ 8 UD 8 UD (=8 tab) 67.5 mg P01BF03_2 P01BF03 Tab O artesunate 50 mg/ 4 UD 4 UD (=4 tab) amodiaquine 0.135 g P01BF03_3 P01BF03 Tab O artesunate 0.1 g/ 2 UD 2 UD (=2 tab) amodiaquine 0.27 g P01BF05_1 P01BF05 Tab O artenimol () 6 UD 6 UD (=6 tab) 20 mg/ 160 mg P01BF05_2 P01BF05 Tab O artenimol (dihydroartemisinin) 3 UD 3 UD (=3 tab) 40 mg/ piperaquine 320 mg

59 GLASS Methodology for surveillance of national antimicrobial consumption

Annex 11 Product origin list

CODE NAME IMP Imported medicines DON Donations/Programs medicines LOC Locally produced medicines for domestic market

Annex 12 Conversion factor list

ATC5 ADMINISTRATION ROUTE FROM TO FACTOR J01CE01 P MU G 0.6 J01CE02 O MU G 0.625 J01FA02 O MU G 0.3125 J01CE08 P MU G 0.6 J01CE09 P MU G 1

Annex 13 Health care sector list

CODE NAME GLO Global sector (public+private sectors) PRI Private sector PUB Public sector

Annex 14 Health care level list

CODE NAME T Total level (community+hospital levels) C Community level H Hospital level

60

World Health Organization 20 avenue Appia 1211 Geneva 72 - Switzerland https//www.who.int/health-topics/antimicrobial-resistance