Orellana García LPO, Kaur K, Brand H, Schröder-Bäck P. Scenario planning: An alternative ap- proach to European Commission for combating antimicrobial resistance by 2050 (Original research). SEEJPH 2021, posted: 06 April 2021. DOI: 10.11576/seejph-4312 P a g e 1 | 11 c ORIGINAL RESEARCH Scenario planning: An alternative approach to European Commission for combating antimicrobial resistance by 2050 Laura Patricia Orellana García1, Kiranjeet Kaur2, Helmut Brand1,3, Peter Schröder-Bäck1 1 Department of International Health, Care and Public Health Research Institute (CAPHRI), Maas- tricht University, The Netherlands; 2 Chitkara School of Health Sciences, Chitkara University, Punjab, India; 3 Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, India. Corresponding author: Laura Patricia Orellana García; Address: Department of International Health, Maastricht University, Duboisdomein 30, 6229 GT, Maastricht, The Netherlands; Email: l.orellanagarcia@student.maastrichtuniversity.nl Orellana García LPO, Kaur K, Brand H, Schröder-Bäck P. Scenario planning: An alternative ap- proach to European Commission for combating antimicrobial resistance by 2050 (Original research). SEEJPH 2021, posted: 06 April 2021. DOI: 10.11576/seejph-4312 P a g e 2 | 11 Abstract Aim: Antimicrobial resistance (AMR) is one of the major health challenges of the future, but the concrete impact of counteracting measures is still unclear. To study possible outcomes within the European Union, a scenario analysis for the year 2050 was performed on the possible influence of the European Commission (EC). Methods: Scenario planning and development of strategies based on different scenarios. Results: Rational use of antimicrobials in animals and humans, surveillance and monitoring, new antimicrobial therapies, travel and globalization, exposure to the environment, and awareness were recognized as the main driving elements. Four Scenarios were developed: An efficient and impli- cated EC sorts out AMR; An implicated but unsuccessful EC withstands AMR; AMR is managed regardless of the EC disinterest; and A neutral and inefficient EC fails to manage AMR. Conclusion: All the strategies developed on the basis of the four scenarios probe for an increase in European Union's dedication to achieve positive outcomes. These include the development of effective legislation and international coordination. Keywords: antimicrobial resistance, European Commission, one health, scenario planning, strate- gies. Acknowledgment: Peter Schröder-Bäck, Helmut Brand and Kiranjeet Kaur’s contribution is co- funded through a grant of the European Commission within the Erasmus+ programme (Project: Prevent it. Project reference: 598515-EPP-1-2018-1-IN-EPPKA2-CBHE-JP). Conflict of interests: None declared. Orellana García LPO, Kaur K, Brand H, Schröder-Bäck P. Scenario planning: An alternative ap- proach to European Commission for combating antimicrobial resistance by 2050 (Original research). SEEJPH 2021, posted: 06 April 2021. DOI: 10.11576/seejph-4312 P a g e 3 | 11 Introduction Since time immemorial, mankind has strug- gled with the control of infectious diseases which are one of the leading causes of death worldwide (1). The COVID-19 pandemic has brought infectious diseases as top priority on the global health agenda, but in general, most of the infections are caused by non-viral agents - the bacteria. Luckily, the develop- ment of antimicrobial agents has remarkably helped for treating these infectious diseases: antimicrobials can kill or inhibit the growth of bacteria by disrupting one or more of their essential functions. However, the indiscrimi- nate and prolific use of antibiotics ensued a selection pressure that led to the emergence of “antibiotic resistant” organisms, resulting in antimicrobial resistance (AMR) (2). It has become a major problem given the slow pace at which new antibiotics are discovered (3). Effective antimicrobial drugs are especially needed for preventive and curative measures such as ensuring complex procedures (sur- geries, cancer treatment, transplants) or pro- tecting patients from fatal diseases (2,4). In 2019, AMR has been named as one of the top ten threats to global health by the World Health Organization (WHO) (5). Apprehen- sions are rampant that AMR may follow sim- ilar patterns as seen in case of epidemic out- breaks developing into pandemics (6). AMR- associated burden can be described as its im- pact on health or on the economy (7). At pre- sent, AMR is estimated to cause 700,000 deaths in the world per year and a cumulative loss of over 88 trillion Euros by 2050 (2,8). Hence, global efforts have been organized to face this challenge. The 2015-WHO Global Action Plan and 2016-United Nations Politi- cal declaration on AMR are some of the latest undertaken actions worldwide (9). In the Eu- ropean Union (EU) 25,000 patients die annu- ally and 1.5 billion euros are expended each year due to AMR (8). Consequently, the EU reinforced the 2001 Community strategy against AMR through the 2011 Commission action plan. With its “One Health” approach, this action plan addresses AMR in humans and animals. Based on previous approaches, the European Commission (EC) also devel- oped guidelines for the prudent use of antimi- crobials in human health (9). AMR preven- tion is also a topic for research and educa- tional projects of the EC, as for example the PREVENT IT project (Risk Management and Prevention of Antibiotics Resistance) that es- tablished a collaboration between European and Indian universities and NGOs for mutual learning (10). To introduce policy interven- tions, evaluations of AMR burden are per- formed through morbidity/mortality and eco- nomic indicators (11). Nevertheless, these indicators are the result of AMR rather than the factors which cur- rently influence it. Thus, to ascertain the best approaches in the EU, it is imperative to acknowledge the factors that will influence AMR by 2050. The present paper aims to de- termine the driving forces of AMR and estab- lish useful strategies through the develop- ment of a series of scenarios. These scenarios will concern the influence of the EU in com- bating AMR by the year 2050. Methods Scenario planning is a technique used for an- ticipating alternative futures. It was origi- nally founded by economic experts to predict large-scale changes. In fact, it is particularly convenient in circumstances with high uncer- tainty. This method is progressively expand- ing in the public health sector since it takes apart the complexity of most public health concerns (12). Accordingly, scenario plan- ning was employed in this study to address AMR intricacy and enhancing key strategies from the EU perspective. Moreover, this method has been applied successfully in the context of EU policies earlier as well. For in- Orellana García LPO, Kaur K, Brand H, Schröder-Bäck P. Scenario planning: An alternative ap- proach to European Commission for combating antimicrobial resistance by 2050 (Original research). SEEJPH 2021, posted: 06 April 2021. DOI: 10.11576/seejph-4312 P a g e 4 | 11 stance, the White Paper on the Future of Eu- rope shows five scenarios for how Europe could evolve by 2025 (13). To execute scenario planning, the process de- scribed by Neiner et al (12) was followed. According to the authors, four steps are needed to develop scenario planning in pub- lic health: (i) Define the sense of purpose; (ii) understand driving forces, key patterns and trends; (iii) develop scenario plots; and (iv) plot strategy, rehearse and converse. Briefly, first of all a relevant objective needs to be es- tablished to define the sense of purpose. In this matter, the impact of AMR on public health was considered, as it has motivated the need for action (14). After all, the EC has rec- ognized AMR threat and works closely with WHO and other partners to accomplish AMR global action plan (15). Besides, it aims the EU to set best example globally (16). Sec- ondly, predetermined and unpredictable forces shaping the objective need to be deter- mined. For this purpose, a literature review was carried out. As a result, key factors, pre- vious actions and current involvement of the EU in AMR were exposed. Next, alternative futures ought to be developed in conformity with the forces formerly established. Hereby, four scenarios were developed based on AMR progress and EC support considering the factors ascertained from the literature re- view. Lastly, valuable strategies should be settled irrespective of the scenario contem- plated. And so, these strategies were ulti- mately included and argued in the discussion section (12). Results Driving forces, key patterns and trends The development of resistance basically in- volves three major determinants: humans, an- imals, and the environment. Resistant bacte- ria arising in humans, animals, or the envi- ronment may spread from one to the other, and from one place to another. It spans inap- propriate antibiotic prescription, uncon- trolled over-the-counter sale of antibiotics, disproportionate use of antibiotics in the food for animals (e.g. livestock, aquatic, pets), and poor sanitation and hygiene (17). Of these, the rational use of antibiotics has a major influence on AMR outcomes. Com- mon infections such as cold, flu are responsi- ble for the majority of antibiotic prescrip- tions, however in reality, most of these infec- tions are caused by viral agents against which antibiotics are ineffective (18). The use of an- tibiotics in these cases is not appropriate, ra- ther it enhances the risk of AMR. Antibiotics also prevail as a prophylactic measure for minimizing the consequence of poor farming conditions and as a growth accelerator (18). To prevent misuse, the EU has published guidelines for the prudent use of antimicrobi- als (19). In this regard, the European Parlia- ment and the Council of the EU issued the EU 2019/6 Regulation that prohibits the use of antimicrobial as prophylactic agent or growth promoter in animals (20). Rational use of an- tibiotics is a predetermined force since it has become a priority for health professionals (21). Surveillance and monitoring are key ele- ments of national action plans on AMR (18). For instance, at EU level, several agencies are involved in AMR surveillance: the European Centre for Disease Prevention and Control (ECDC), the European Medicines Agency (EMA), and the European Food Safety Agency (EFSA). Basically, ECDC is respon- sible for coordinating two surveillance net- works (EARS-Net and ESAC-Net), while EMA and EFSA publish annual reports on AMR (18). These are predetermined forces - since these agencies are expected to continue with their responsibilities. Public awareness is another key element in combating AMR. The results of Price et al (22) substantiated poor understanding of Orellana García LPO, Kaur K, Brand H, Schröder-Bäck P. Scenario planning: An alternative ap- proach to European Commission for combating antimicrobial resistance by 2050 (Original research). SEEJPH 2021, posted: 06 April 2021. DOI: 10.11576/seejph-4312 P a g e 5 | 11 AMR in the general population. As a matter of fact, the 2018 Eurobarometer indicated 57% of Europeans were uninformed that an- tibiotics are ineffective against viruses (18). This unawareness endorses antibiotics’ mis- use and so AMR. Hence, ECDC established the European Antibiotic Awareness Day (EAAD) which aims to support the correct use of antibiotics through national campaigns (16). Though raising AMR awareness per- haps entail a predictable force, its effective- ness is certainly unpredictable. The discovery of new antimicrobials and di- agnostic techniques will significantly impact AMR (23), therefore more investment is needed in basic science (18). For this reason, one of the main pillars of One Health Action Plan focus on boosting research, develop- ment and innovation (9). In this regard, the EU is developing in coordination with indus- try for development of new antibacterial agents under the COMBACTE-MAGNET project (24). Despite the investment, it is un- predictable when new antimicrobials will be ready and if so, what will be their efficacy against AMR strains. The relevance of the interaction between chemicals (antimicrobials, heavy metals, and biocides) and pathways (industrial wastewater, animal manure) has also been emphasized in contributing to the spread of AMR. It seems that strict environmental reg- ulations are needed in the development of AMR national action plans (25). The EU acknowledges that strong evidence is needed to counteract the incomprehension of the en- vironment role in AMR. To fill this knowledge gap, specific actions (such as strengthening the role of the Scientific Com- mittee on Health and Environmental Risks (SCHER) on AMR matters) have been in- cluded in the EU One Health Action Plan (9). Despite the EC engagement in the environ- mental area, the success of this approach is yet unpredictable. Lastly, travel and globalization have allowed newer opportunities for cross-transmission of AMR (23). Visitors from developed coun- tries such as USA often show colonization or infections with KPC-, VIM-, OXA-48- and especially NDM-producing Enterobacteri- aceae, upon travel to countries such as Greece, Israel, Turkey and Morocco and the Indian subcontinent (26). Amongst various categories of visits, medical tourism is spe- cifically linked to the spread of AMR. People from developed countries usually undergo several types of surgical procedures in devel- oping countries such as India and China due to relatively low treatment costs and shorter waiting times for surgeries. Travel and glob- alization are unpredictable driving forces since their course and trends are likely uncer- tain. Scenario plots Four scenario plots have been developed, based on the anticipated futures resulting from AMR progress and EC support. The dif- ferent scenario plots are presented in Table 1 and 2. The first two scenarios (‘An efficient and im- plicated EC sorts out AMR’ and ‘An impli- cated but unsuccessful EC withstands AMR’) assumed a strong EC involvement, whereas in the last two (AMR is managed regardless of the EC disinterest and A neutral and inef- ficient EC fails to manage AMR) indicates that there is no engagement of the EC to en- counter AMR. Despite the level of support provided by the EC, in the first and third sce- nario (An efficient and implicated EC sorts out AMR and AMR is managed regardless of the EC disinterest) it is assumed AMR has been addressed appropriately. On the con- trary, the second and fourth scenario (An im- plicated but unsuccessful EC withstands AMR and A neutral and inefficient EC fails to manage AMR) assumed an inefficient management of AMR. Orellana García LPO, Kaur K, Brand H, Schröder-Bäck P. Scenario planning: An alternative ap- proach to European Commission for combating antimicrobial resistance by 2050 (Original research). SEEJPH 2021, posted: 06 April 2021. DOI: 10.11576/seejph-4312 P a g e 6 | 11 Table 1. Scenario planning for AMR in view of the EC Table 2. Scenario planning for AMR in view of the EC An efficient and im- plicated EC sorts out AMR An implicated but unsuccessful EC withstands AMR AMR is managed regardless of the EC disinterest A neutral and ineffi- cient EC fails to manage AMR U n p r e d ic ta b le f o r c e s A M R a w a r e n e ss The EC encouraged MS to raise effective awareness among the population through the increase of national campaigns. People are conscious of the use of antibiotics and follow accurately healthcare professionals’ instruc- tions. The EC supported MS in developing multiple national campaigns to raise AMR mindfulness. Even so, the interven- tions did not have the desired impact and the public still use antimicrobials indis- criminately. The EC did not en- courage MS to in- crease the number of national campaigns to raise AMR aware- ness. However, the general public is more conscious about the AMR problem and they use antibiot- ics less indiscrimi- nately, although mis- use still exists. The EC failed to en- courage and support MS to raise AMR awareness through sufficient and effective national campaigns. Citizens misuse antibi- otics which have in- creased the number of resistant pathogens. An efficient and im- plicated EC sorts out AMR An implicated but un- successful EC with- stands AMR AMR is managed regardless of the EC disinterest A neutral and ineffi- cient EC fails to manage AMR P r e d e te r m in e d f o r c e s R a ti o n a l u se i n a n im a ls a n d h u m a n s The EC extended the guidelines and intro- duced stricter measures regarding the use of antimicrobi- als. The broad use of antimicrobials de- creased and they are uniquely provided when indicated in guidelines. The EC extended the guidelines and introduced stricter measures for anti- microbials use. Still, pro- fessionals do not follow the guidelines and measures established. Antimicrobials are used irrationally which has re- sulted in an increase of AMR. The EC did not ex- tend the guidelines and measures re- garding the use of antimicrobials. De- spite this, profes- sionals are following outdated guidelines. AMR has slightly increased but not as much as it was ex- pected. The EC did not ex- tend the guidelines and measures regard- ing the use of antimi- crobials. Besides, pro- fessionals are not fol- lowing the guidelines and measures. S u r v e il la n c e a n d m o n it o r in g Surveillance and eval- uation of AMR have been performed cor- rectly. Useful infor- mation has been gath- ered which allowed to develop appropriate strategies to confront AMR. Surveillance and evalua- tion of AMR have been performed correctly and more agencies have been involved to complete this task. Despite the infor- mation gathered, it has not been used appropri- ately to developed useful strategies to approach AMR. Surveillance and evaluation of AMR have failed to pro- vide useful infor- mation. However, policymakers have been able to use the little information gathered to improve some strategies and developed useful in- terventions. Surveillance and eval- uation of AMR have failed to provide use- ful information. The EC has lost interest in monitoring AMR, there is no pressure from the European Parliament or the EC. The real status of the AMR situation is not known. Orellana García LPO, Kaur K, Brand H, Schröder-Bäck P. Scenario planning: An alternative ap- proach to European Commission for combating antimicrobial resistance by 2050 (Original research). SEEJPH 2021, posted: 06 April 2021. DOI: 10.11576/seejph-4312 P a g e 7 | 11 N e w a n ti m ic r o b ia l th e r a p ie s The EC has constantly been investing in AMR research. The investment has pro- vided good results, new antibiotics have been discovered and new diagnostic tech- nologies developed. AMR exists but there are effective resources to deal with it. The EC has con- stantly been investing in AMR research. However, the devel- opment of new anti- microbials and diag- nostics has not im- proved considerably. New advances have been made but not sufficiently to solve the problem. The EC decreased the investment in re- search in AMR. The development of new therapies and diag- nostics has slowed down. Despite this, new technologies de- veloped for other health problems have been useful to deal with AMR and re- duce its impact. The EC stopped the investment in research, and no new develop- ment has been achieved. Old Antimi- crobials are still used as first and second-line treatments. Health pro- fessionals have to deal with new AMR patho- gens. A M R e x p o su r e t o t h e e n v ir o n m e n t The EC has been working to involve en- vironmental regulators in AMR national ac- tion plans. Also, their coordination with stakeholders has im- proved. The degrada- tion of antimicrobials in wastewater is strictly controlled and treated. No antimicro- bials are released to the environment. The EC has been working to get envi- ronmental regulators to be more involved in AMR national ac- tion plans. However, their coordination with stakeholders is still insufficient. New regulations are con- sidered to be imple- mented regarding wastewater, but no steady action has been yet taken. The EC did not boost the involvement of environmental regu- lators in AMR na- tional action plans. Nonetheless, there is coordination between environmental regu- lators and other stakeholders. They achieved to develop strategies to mini- mize AMR impact in the environment. The EC did not boost the involvement and coordination between environmental regula- tors and stakeholders. National action plans did not include AMR's impact on the environ- ment. Antimicrobials are constantly released to the environment since there is no regu- lation to control it. T r a v e l a n d g lo b a li z a ti o n Tourism increased in the last years. The EC has been working to endorse early screen- ing and control measures to tourist ar- riving from AMR en- demic areas. These measures have been successfully applied and so, fewer AMR pathogens have been spread. The EC encouraged new control measures and provided addi- tional guidance on early screening for tourists returning from AMR endemic areas, yet they were not strongly fol- lowed, and several AMR strains have been locally spread. The EC has not con- sidered the need of new guidelines re- garding early detec- tion or additional measures in tourists. Nonetheless, healthcare profes- sionals have been able to detect certain carriers and limit the spread of imported AMR strains. There EC ignored tourism as a AMR threat and conse- quently, no measures have been considered nor proposed to super- vise the transit of tour- ist arriving from AMR endemic areas. This situation has boosted the spread of AMR strains to different re- gions. Discussion The ongoing COVID-19 pandemic has taught us a big lesson that how devastating non- treatable infectious diseases can be (27). On similar league, AMR bears the proficiency of attacking us as an epidemic or pandemic. An estimate by WHO suggests that approxi- mately 10 million deaths will happen due to AMR by 2050. Although just a forecast, some of the scenarios described could be as- sociated with this number of deaths. To de- crease the odds of these deaths becoming a reality, actions must be taken on priority. Therefore, the potential influence of driving forces has been described in the scenario Orellana García LPO, Kaur K, Brand H, Schröder-Bäck P. Scenario planning: An alternative ap- proach to European Commission for combating antimicrobial resistance by 2050 (Original research). SEEJPH 2021, posted: 06 April 2021. DOI: 10.11576/seejph-4312 P a g e 8 | 11 plots to better understand the ways to combat AMR. Encouraging legislators to introduce stand- ards and procedures to assure sensible use of antimicrobials will be useful (19). Antibiotics could be restricted with a similar approach narcotics and psychotropics are controlled (regulated by the Single Convention on Nar- cotic Drugs of 1961 and the Convention on Psychotropic Substances of 1971). The de- velopment of these “Antibiotic Conventions” could shift the prescription of antibiotics as a first-line treatment to every possible infec- tion. Nevertheless, to achieve this type of covenant a high level of international agree- ment is required. Stakeholders would clearly benefit from this consensus and of these, so- ciety also plays a fundamental role. Public awareness is an influential factor on AMR. Thus, further efforts should be considered to increase population’s consciousness about AMR threat: diversification of AMR cam- paigns in diverse channels such as TV, radio, or social media that could successfully raise public awareness. In light of newer antibiotics, the development of effective antibiotics against resistant strains is the need of the hour. A fixed amount of money provided by the EC to industry could be established as funding to foster new antibiotics discoveries. Promoting partner- ship with industries will also improve the likelihood of developing better diagnostics to determine the etiologic agents of the diseases and, consequently, prescribe antibiotics only when necessary. Likewise, the use of artifi- cial intelligence in AMR surveillance and monitoring would allow to analyze existing data more precisely and consequently im- prove outcomes through strategies adapted to each circumstance. Tourism also represents a relevant threat to the spread of AMR strains: tourists may ac- quire AMR pathogens in their journeys and subsequently spread them in their country of origin. Early detection of carriers and control measures, in combination with international cooperation are strategies which could be beneficial, if they are successfully applied (23,28). On the other hand, it is necessary to emphasize the connection between AMR and the environment. On this ground, legal measures could be established to control wastewater treatment, followed by regular in- spections to assure that legislation is properly applied. In general, the strategies developed from each scenario imply that the outcomes would likely be beneficial if there is an increase of commitment and coordination between stakeholders, especially from the EC. Some of the strategies established have been com- pared with conventions already applied to other health challenges, such as the Psycho- tropic and Narcotic Drug Conventions. Nonetheless, to achieve these methods, fur- ther collaboration and coordination are needed not only among Member States but also at international level. The EU-India col- laboration contributing to this global perspec- tive (10). The global position also empha- sizes the important role the EU plays in this global health challenge and the advantageous outcomes that could be achieved if the EU is fully involved in slowing down AMR. On the other hand, the results have shown that the EC could address the driving forces of surveillance and monitoring, environmen- tal AMR, treatment innovation, and tourism by introducing new legislation. EU legisla- tion can have a significant impact, not only within the Member States but also outside its borders. In fact, the EU is currently endorsing AMR measures in third countries through different actions, like promoting AMR-re- lated standards in its bilateral Free Trade Agreements (FTAs) (9). These actions under- pin the role of the EU as a global actor in the Orellana García LPO, Kaur K, Brand H, Schröder-Bäck P. Scenario planning: An alternative ap- proach to European Commission for combating antimicrobial resistance by 2050 (Original research). SEEJPH 2021, posted: 06 April 2021. DOI: 10.11576/seejph-4312 P a g e 9 | 11 AMR challenge and highlights, again, the im- portance of developing and reinforcing inter- national collaboration. Limitations: The initial inquiry necessary for determining the trends and driving forces was not based on a systematic literature review. Scenario planning is a method based on as- sumptions and therefore subject to bias, yet the non-systematic research of driving forces increases the risk of bias. Besides, some of the driving forces, though acknowledged, were not included in the scenario planning as per the scope of this paper. For instance, the use of vaccination has shown positive effects in reducing AMR, although its success has been historically under-recognized so far (29). 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