We first present an overview of the irrational use of antibiotics in Iran and, then, describe the system as a CAS using the CAS observatory tool.
An overview of the irrational use of antibiotics in Iran
Generally, the irrational use of antibiotics in Iran was acknowledged by almost all interviewees, although some also believed that some progress had been achieved in recent years. The total percentage of prescriptions containing antibiotics has decreased, some new pharmaceutical protocols have just been enforced in hospitals to rationalize the use of most expensive antibiotics and many researches have been done in this field. Nevertheless, the participants pointed to so many case of the irrational use of antibiotics. Patients’ adherence to antibiotic therapy is estimated medium to low, they do not follow the instructions properly and do not complete the antibiotics therapy course. Antibiotics self-medication is prevalent especially when patients suffer from common cold. Many community pharmacies deliver antibiotics to patients and customers without prescription and therefore antibiotics are easily accessible to public. Physicians usually prescribe antibiotics irrespective of medical guidelines or laboratory tests because of some constraints such as time and patients’ insistence. These constraints sometimes lead to inappropriate dosing, improper combination therapy and irrational prescription of injectable antibiotics. All these behaviors have ultimately culminated in a high incidence of antibiotic resistance.
Antibiotics use system as a CAS
Agents and their interactions
We identified several diverse and heterogeneous agents regarding the use of antibiotics in Iran, organized in subsystems or groups like medical universities, hospitals, patients, etc. Moreover, some interviewees suggested that significant diversity could be seen in similar agents. For instance, physicians, pharmacists and patients’ perception and behavior related to antibiotics are not always similar as they stem from different level of knowledge or attitude, experiences and individual and organizational governing values and rules.
All these agents can fall into two major categories: supply-oriented agents and demand-oriented agents. Supply-oriented agents refer to all agents that can provide antibiotics to end users (can be patients or not) or play a role in the process of supplying, for instance by regulating the procedures or training physicians. Demand-oriented agents, on the other hand, refer to all agents that are prone to use antibiotics, both prescribed and unprescribed, or, like the media, can alter the behavior of antibiotic use in either side. It should also be noted that some agents like physicians can be fuzzy members of both categories as they can affect both the supply and demand sides of antibiotic use. Within these arrangements, agents can be characterized by their properties, role, importance or power and objectives [see Table 1 file].
Table 1- Agents, their properties, role, power, and objectives
Agents
or subsystems
|
Role
|
Related components
|
Importance/power
|
Objectives/ incentives
|
Supply-oriented
|
Ministry of health and medical education (MOH)
|
It is the main policy-making and stewardship agent that decides about macro health policies. It also regulates and finances all service provisions in healthcare
|
Deputy of curative affairs, deputy of education and deputy for health. Some components like medical universities existing all provinces all around the country, are defined as a major and separate agent.
|
The most important governmental agent that oversees all the actions and processes in health care system and is in charge of all things related to public health.
|
Providing health and hygiene to all citizens.
|
Iran Food And Drug Administration (IFDA)
|
Supervising and regulating all the processes of manufacturing, distributing, and use of antibiotics. It is authorized and financed by MOH
|
The National Committee on Rational Use of Drugs (NCRUD),
General directorate of Pharmaceutical and narcotic affairs
|
It is the most substantial supervisory body that directly controls all the processes of supply and access to antibiotics. It makes policies related to access to antibiotics and compiles pharmaceutical guidelines through collaborating with other related bodies. It is also responsible for the rational use of all drugs, especially antibiotics.
|
Enabling access to effective and safe medicines in a rational way.
|
Basic health Insurance companies
|
They reimburse antibiotic drugs.
|
There are three major basic public insurance companies in Iran. Besides National health Insurance called Iran Health Insurance Organization (IHIO) and Social Security Insurance (SSI), there is also Ministry of Defense Health Insurance Organization. There are also many private insurance companies, but they are not usually considered as major players
|
They are the main enforcing levers of health policies in Iran. They can rationalize the use of antibiotics by developing limitations and special regulations for reimbursing antibiotics.
|
Trying to minimize their cost.
|
Medical universities
|
They are authorized by MOH. They educate and train physicians, pharmacists, specialists, and other healthcare professionals who can order or deliver antibiotics.
|
Vice chancellor of Food and Drug administration in medical universities, Educational hospitals and pharmacies, professors, students and medical residents
|
The power of medical universities is pretty high because MOH and IFDA enforce their supervision of prescribing and delivering antibiotics through Food and Drug Departments of different medical universities. All departments have a RUD committee. They periodically check upon physicians under their supervision to ensure their acceptable prescription practices and provide feedback to them.
Additionally, they play a critical role in promoting physicians and pharmacists’ knowledge and practice of antibiotics by continuing medical education (CME) programs. they can also supervise all promotional activities of pharmaceutical companies in hospitals, pharmacies and clinics, etc.
|
Training qualified and knowledgeable physicians, pharmacists and other health care professional. Helping health care professionals maintain competence and learn about new and developing areas of their field.
|
Research centers
|
Conducting clinical and non-clinical researches related to the rational use of antibiotics.
|
-
|
The outcome of their researches may influence two main processes: policy-making and antibiotic prescription.
|
Communicating and collaborating with policy-makers and prescribers adequately. Carrying out feasible and practical researches.
|
Islamic Republic of Iran Medical Council (IRIMC)
|
IRIMC is the largest national non-governmental organization in which all health care professionals (except nurses) have to register to be granted permission to practice in the country. It regulates health care professionals’ collaborations with other associations. It has developed many regulations and guidelines related to medical practice standards.
|
It has more than 190 branches all over the country in different cities.
|
It can play an important supervisory role in physicians and pharmacists’ practices. Additionally, it can affect the physicians’ prescription behaviors through their contribution to the development and enforcement of guidelines as well as educational programs.
|
Improving and modifying medical affairs in Iran. Supporting patients’ and health care professionals’ rights. Promoting medical knowledge in Iran.
|
Scientific and guild NGOs
|
Providing educational and research services. They support healthcare professionals’ rights.
|
Many scientific and non-scientific NGOs are practicing in different fields of medical sciences.
|
They play a significant role in other health care professionals’ behavior such as nurses, dentists, etc.
They also enforce regulations, influence antibiotic prescription practices, and make connections between different groups of healthcare professionals.
|
Improving education, training and research services. Protecting physicians and pharmacists’ monetary and non-monetary rights.
|
Pharmaceutical companies
|
Producing or importing necessary pharmaceuticals of the country. Introducing, providing and promoting antibiotics to prescribers and pharmacies through diverse promotional activities.
|
It includes many manufacturing and importing companies.
|
They can highly affect both demand and especially supply sides of the antibiotic market. They promote their products through different ways such as giving free samples, discounts, gifts, etc.
|
Making more profit through grabbing and maintaining more market share.
|
Prescribers
|
They prescribe antibiotics to the patients.
|
It includes physicians (General Practitioners or specialists), dentists and midwives.
|
After MOH, they are the second important agent in both supply- and demand-oriented group agents. They determine the number and quality of antibiotic prescription.
|
A wide range of interests from enhancing rational use of antibiotics and patients’ quality of life to monetary objectives and visiting more patients.
|
Hospitals
|
Providing in-patient care service and also most of the time, out-patients’ services.
|
Physicians, nurses, clinical pharmacists, Pharm-D, pharmacotherapy committee, and antibiotics stewardship committee
|
Their practice highly affects the volume and the quality use of a wide spectrum of injectable antibiotics.
|
Controlling antibiotic use, improving the rational use of antibiotics in order to prevent antimicrobial resistance at hospitals
|
pharmacists
|
Delivering antibiotics to patients and to the general public. They also have to explain and give consultation to patients about the use of antibiotics in terms of how to use, interactions and side effects, etc.
|
-
|
Irrespective of codes of action, they sometimes provide antibiotics to the public and patients over the counter. They occasionally collaborate with pharmaceutical companies to sell more antibiotics. They can also collaborate with physicians to prescribe more antibiotics.
|
Providing good service delivery and maximizing their profit.
|
Demand-oriented
|
mass media
|
Improving public knowledge about antibiotics through educational programs and contents.
|
TV, social networks like Instagram, telegram, Facebook, etc.
|
They can highly affect public knowledge, attitudes about antibiotics. They also help to modify the general public’s life style and alter their perception of antibiotics, physicians and pharmacists.
|
To attract and maintain more audiences.
|
Patients and public
|
use antibiotics (final consumer)
|
Patients, patients’ families and friends, public population
|
They are the most important agent on the demand-side. Their health literacy, knowledge, perceptions, expectations and experiences highly affect antibiotic use.
|
Living better and more comfortably. Having the best treatment in the world for their illnesses.
Having the lowest cost services.
|
After the original mapping of agents, we could breaking down the whole system into four circles as layers or subsystems, into four interdependent layers as subsystems (Fig1). Circle 1 comprises of Ministry of Health (MOH), Iran Food and Drug Administration (IFDA) and insurance companies that make policies, regulate the system, reimburse and provide access to antibiotics. Circle 2 consists of those agents who monitor the implementation of regulations and guidelines, help circle 1 to enforce the regulation and make better policies by providing necessary evidence. Circle 3 includes pharmaceutical companies and pharmacies who produce and distribute antibiotics. However, the core functions of supply and use of antibiotics take place in circle 4. Physicians include general practitioners and specialists, patients, public population, pharmacies and hospitals are overlaid by this circle. Although these circles are operating at different levels and can be broken up, they are highly interdependent with overlaps. Most participants argued that most of current solutions to tackle the irrational use of antibiotics in Iran have failed to adequately take into account all agents, their role and power.
“See Fig1. Subsystems of antibiotic use in Iran”
Nested structured Interaction
Data analysis showed that there are diverse and several interactions and interaction patterns between agents (stakeholders) in antibiotic use in Iran, playing out in a nested structure and also a network system. These interaction identified to be influential in decision making and behaviours in regard to prescription or use of antibiotics, based on rules enforced or information exchanged through these interactions.
We identified three patterns of interactions between agents. Type one represents governance and supervisory-oriented top-down relationships that regulate the activities, supervise the procedures and finance or reimburse medical costs; a good case in point can be several formal governance-oriented and rule-based relationships of MOH with IFDA, top down interactions of medical universities with hospitals, or financial and legal relationships of insurance companies with physicians and pharmacies regarding the reimbursement of service provision and medical costs. Type two represents interactions related to service provision, where the main action of antibiotic consumption occurs. Several informal and formal relationships between physicians, pharmacists, patients and hospitals are subsumed under this rather broad category. Finally, type three embodies reciprocal relationships, where agents have interactions based on professional collaboration or contract-based corporation. For instance, there are collaborative interactions between MOH and IFDA with medical universities and research centers, pharmaceutical companies contract research centers to conduct their clinical trial researches, IFDA have interaction with scientific Non-Governmental Organizations (NGOs) or Islamic Republic of Iran Medical Council (IRIMC) or academia, insurance companies send prescription information which IFDA or MOH or medical universities have requested, hospitals can provide data and information which research centers and medical universities need for their researches, and pharmaceutical companies have many formal and informal relationships with physicians and pharmacies. Through all these types of interactions, information and financial resources get exchanged, regulations are enforced and antibiotics are delivered to patients or the general public as a whole. Figure 2 shows the contribution of agents’ interactions to the formation of a nested and multilevel system.
“See Fig2. Main agents’ interactions in antibiotic use in Iran and their contribution to the formation a networked interaction structure
Many participants believed that interactions between key stakeholders in antibiotic use system in Iran were often insufficient, ineffective or non-systematic. For example, interviewees made a point of highlighting the discontinuous and insufficient reciprocal interactions between research centers and policy-making entities like MOH, IFDA, insurance companies and research centers. Inadequate interactions of IFDA with other agents such as IRIMC were mentioned by majority of participants. Lack of adequate supervision on prescribing and delivering antibiotics, incomplete implementation of programs and improper enforcement of rules and regulations were identified as the consequences of current ineffective interactions and inadequate coordination between different parts of the MOH and the whole system of antibiotics use in Iran.
Information flow
Almost all respondents were dissatisfied with the current information flow of the system. Data analysis showed Information regarding antibiotic use circulates inefficiently and inadequately through the systems. For example, insurance companies send prescription-related information to IFDA or MOH, but there have been some logistic problems in recent years that have impeded data transformation. MOH and IFDA not always receive information about antibiotic use statistics from hospitals or medical universities, and some participants revealed that this information flow was sporadic and erratic. Many people in FGDs complained about the incomplete information about antibiotic use imparted to them by physicians and pharmacists. Physicians and pharmacists are supposed to educate patients about the administration of antibiotics and how they should be used while they are prescribing and delivering antibiotics. These improper relationships of patients with physicians and pharmacists may consequently lead to irrational use of antibiotics, as an instance patients do not complete treatment course and discontinue antibiotics use as they get better. Respondents working for research centers or scientific NGOs stated that despite their willingness to collaborate with IFDA or MOH to conduct useful researches and participate in health decision making, the stage had not been set for the smooth flow.
Moreover, many participants criticized the quality and accuracy of information about antibiotics production and distribution run in the system, caused by ineffective and insufficient interaction between IFDA and pharmaceutical companies. Some interviewees argued that sometimes information circulation is done through informal and non-documented channels, and so much of officially documented information exchange slips unnoticed. Additionally, there are some logistic obstacles in the way of data collection and information integration that have made the information flow problematic.
Feedback loops
The main identified formal feedback mechanism in the system of antibiotic use in Iran is about antibiotic prescription information which is yielded through analyzing physicians’ prescription and mostly prepared by basic insurance companies. Such information is sent from insurance companies to IFDA or the vice chancellor of the Food and Drug administration in different medical universities. They report RUD indicators such as the mean item per prescription and the percentage of prescriptions containing antibiotics. Analyzing this information, regulatory bodies evaluate their programs and the effectiveness of their practices toward the rational use of antibiotics. In some cases, they send feedback reports to physicians who have not met prescription indicators and ask them to adhere to guidelines and regulations. Moreover, no systematic feedback mechanisms were identified from MOH, IFDA or insurance companies to prescribers and other practitioners or vice versa in the system
There are some informal and even not easily observable feedbacks that form the behavior of the system as follows:
Antibiotic resistance, caused by irrational use in human and many other variables not included in this study, increases treatment failure of infectious diseases and so decreases patients’ proper experience with antibiotics. This in turn can negatively influence patients’ adherence to the treatment course, encouraging them to discontinue antibiotic therapy, or consume more potent antibiotics, and also may decrease physicians’ adherence to medical guidelines, which can in turn increase irrational prescription of antibiotics and the threat of antibiotics resistance.
Patients’ experience with previously used antibiotics may affect the patient-doctor relationship and their trust in physicians as well. Many respondents said that in many cases physicians prescribe antibiotics irrationally because patients do not trust them and insist on receiving newer or more antibiotics. Physicians may receive feedback from patients who are prescribed antibiotics by following their therapeutic responses and observing their symptoms. The patient-doctor relationship influences patients’ tendency toward visiting physicians and can cause more self-medication tendency with antibiotics, which can in turn reinforce the quality of the patient-doctor relationship through irrational use of antibiotics and more treatment failure. In addition, providing antibiotics over the counter worsens self-medication through increasing public access to antibiotics without prescription.
Rules and values
Different types of formal rules are identified in antibiotic use including pharmaceutical and medical guidelines and protocols, WHO and international guidelines, laws of IRIMC, codes and regulations of insurance companies, and codes of actions and regulations developed by MOH. Most of them are authorized by MOH and publicly accessible. However, it was identified that they are not always followed by the agents.
Interviewees who were clinical pharmacists argued that not all physicians easily adhere to evidence-based medicine and collaborate with clinical pharmacists to change their antibiotic prescriptions. Some defy pharmaceutical guidelines and dismiss them in favor of their own experiences. Clinical pharmacists believed that physicians’ different following rules behaviors may be also influenced by their prior interaction with pharmacists, and also health authorities.
Prescription and use of antibiotics were governed by the agents’ perception of formal rules, which can be termed internalized rules. According to some participants, physicians and patients follow their internalized rules more obediently than central and formal regulations. Even some sub systems like hospitals have their own internalized official regulations and guidelines. For example, some hospitals have developed their own regulations and guidelines about infectious disease, derived from formal regulations and adapted to their contextual properties. We observed that pharmaceutical protocols were performing well in some private and public hospitals and were accepted by clinical pharmacists and Infectious disease specialists. However, some hospitals dismissed them because they believed pharmaceutical protocols should be internally developed on the basis of the internal context of hospitals or there should be a reasonable room for change and adaptation.
However, results of the study revealed that this self-organizational behavior of sub systems are not well regarded by regulatory bodies in Iran.
In addition to rules, organizational, professional and individual values were also recognized as contributing to governing certain types of behavior. They included organizational, professional and individual values. For example, insurance companies have clear and well-established credit and blame mechanisms which aim to restrict physicians’ over-prescription of antibiotics. Most participants agreed that rational use of antibiotics greatly matters to governmental authorities due to the significance of antimicrobial resistance, which partly explains the establishment of Rational Use of Drugs committees in vice chancellors of Food and Drug administration and hospitals. Likewise, among RUD indicators, the antibiotic use standard has always been an important indicator for MOH. However, it seemed to be controversial, some respondents argued that the importance of RUD committees had declined for MOH and antibiotics have lost their priority. For example, except in insurance companies, there are no credit or blame mechanisms in governmental organizations related to the rational use of antibiotics and many respondents believed that their efforts to rationalize antibiotics use were not appreciated as much as they deserved. Some argued that the reason of failure to achieve the whole goals of NCRUD was the lack of support of its organizational position by MOH.
In addition to organizational and professional values, individual values also influence the patients and physicians’ behaviour in regard to antibiotics. For example, some interviewees stated that sometimes people including physicians may have enough knowledge about the importance of rational use of antibiotics but their knowledge did not translate into attitude and practice.
Some participants noted that the magnitude of the rational use of medicines varies from person to person among policy makers and health care managers. During some periods of times, it might have attracted considerable attention and, under a different person’s management, it might have been consigned to oblivion.
Dependent, diverse and multifactorial behaviors different of agents
We classified four major behaviors in antibiotic use system conducted by key agents, all influenced by their information, rules, values, resources, feedbacks and interaction with other agents.
Physicians’ prescription behaviours- Variation in physicians’ prescription behavior was expressed by a wide range of participants. Generally all participants believed that physicians’ prescription behavior is influenced by the quality of their interactions with patients, like their efforts to satisfy patients. Patients’ satisfaction seemed to be more important in contexts where physicians compete for more patients and more income. Noting the effect of context, some FGD participants believed that physicians exhibit different behaviors in public and private sectors. Additionally, some physicians argued that they are faced with time constraints in some settings and do not have enough time to explain and convince patients that they do not need antibiotics. However, some people in FGDs reported contrary experiences with physicians who had spent reasonable time visiting them in spite of a long queue of patients. These co-evolutionary physicians’ behaviors makes difficulties to predict the emergent behaviour of the whole system
Pharmaceutical companies and pharmacies behaviors- Data analysis of information provided by this study indicated that the behaviors of pharmaceutical companies and community pharmacies depend on many factors which may not necessarily be relevant to their knowledge, the health care system or its rules, and may even be exogenous to it. For example, their practices are highly dependent on their income and so the economic, political and even the international communication conditions of the country. In recent years, some technical and international communication problems have impeded pharmaceutical export and many pharmaceutical companies have lost their niche market in the Middle East. As a result, they have produced antibiotics in excess of domestic use such that their inventories overflow with antibiotics, and so more efforts to sell antibiotics. Besides external limitations, there have been some restrictions imposed by MOH and IFDA on the procurement of the active pharmaceutical ingredients of antibiotics and pharmaceutical pricing, which can in turn further compound the situation. These forces altogether have driven companies to adapt themselves to an unpleasant situation by enhancing antibiotic sales through promotional activities. It was reported by participants that pharmaceutical companies sometimes provide some products like antibiotics free of charge to pharmacies as part of their promotional activities, offering financial incentives for physicians to over-prescribe antibiotics. These promotional activities seemed to be the most pressing concern repeated by almost all policy makers and prescribers interviewed in this study. On the other hand, economic pressures encourage pharmacies more to deliver antibiotics over the counter to the public in order to increase their revenues. Although these marketing strategies have increased the total use of antibiotics, they can be understood as an adapting behavior of companies and pharmacies.
Policy making and implementation behaviors- Several interviewees discussed that depending on policy makers’ willingness to earn short-term outcomes, personal preferences, characteristics and responsibility, contextual constraints and experiences, they may show different behaviors at different health care settings. In addition to personal preferences, it was argued that occasional crises, the context and limitations has led to different rule adherence behaviors.
Patients’ antibiotic use behavior- Data analysis revealed that antibiotic consumption behaviour of people are determined by many factors such as socio-economic situation, their perception of and belief in physicians, their perception of self-medication, antibiotics benefits and hazards, and their medical history. For example, some participants choose supplementary medicines and herbal pharmaceuticals when they catch a cold because they believe that herbal pharmaceuticals are more effective than antibiotics and chemical medicines; however, some others cannot implicitly trust herbal medicines because of their unknown side effects. According to their experiences, some people believed in the efficacy of antibiotics, while others thought that their efficacy is not overweighed by their side effects.