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.
Confirming the irrational use of antibiotics in Iran
Generally, the irrational use of antibiotics in Iran was also acknowledged by almost all interviewees, although some argued that some progress had been achieved in recent years.. Many participants estimated that patients’ adherence to antibiotic therapy was estimated medium to low, as they did not follow the instructions properly and did not complete the antibiotics therapy course. Antibiotics self-medication were identified to be prevalent especially when patients suffered from the common cold. They also reported that many pharmacies deliver antibiotics to customers without prescription and therefore antibiotics were easily accessible to the public. It was identified that, for a variety of reasons such as patients’ insistence and satisfaction, physicians usually prescribed antibiotics irrespective of medical guidelines or laboratory tests because of some reasons such as time and patients’ insistence. These factors sometimes led 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.
Considering antibiotics use system as a CAS
Agents and their interactions
We identified several diverse and heterogeneous agents (stakeholders) regarding the use of antibiotics in Iran, organized in subsystems or groups of medical universities, hospitals, patients, etc. Moreover, some interviewees suggested that significant diversity could be seen in similar agents. For instance, perceptions and behavior of physicians, pharmacists and patients in regard to antibiotics are not always similar as they stem from a different level of knowledge, 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 antibiotics use on either side. It should also be noted that some agents can be shared members of both categories as they can affect both the supply and demand sides of antibiotics use. These agents include the Ministry of Health (MOH), Iran Food and Drug Administration (IFDA), prescribers, and hospitals. Within these arrangements, agents can be characterized by their properties, roles, 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 break down the whole system into four interdependent layers as subsystems (Fig1). Circle 1 comprises of MOH, 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 the necessary evidence. IFDA is present in both circle 1 and circle 2, because it contributes to both policy making and supervision. Circle 3 includes pharmaceutical companies and pharmacies that 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, the public, pharmacies and, hospitals are overlaid by this circle. Pharmacies are distributing antibiotics and ensure access to them, therefore, they are placed in both circle 3 and circle 4. Besides, hospitals are potentially very important agents that produce information and pieces of evidence needed for decision makings. Therefore, they are present in both circle 2 and circle 4. 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 the current solutions to tackle the irrational use of antibiotics in Iran have failed to adequately take into account all agents, their role and power.
Nested structured Interaction
Data analysis showed that there are diverse and several interactions and interaction patterns between agents (stakeholders) in antibiotics use in Iran, playing out in a nested structure and also a network system. These interactions identified to be influential in decision making and behaviors regarding prescription or use of antibiotics, based on rules enforced or information exchanged through these interactions. Figure 2 shows the contribution of agents’ interactions to the formation of a nested and multilevel system.
We identified three patterns of interactions between agents. Type one represents governance and supervisory-oriented top-down interactions that regulate the activities, supervise the procedures and finance or reimburse medical costs. For example, there can be several formal governance-oriented and so rule-based interactions of MOH with IFDA, top-down interactions of medical universities with hospitals, or financial and legal interactions of insurance companies with physicians and pharmacies regarding the reimbursement of service provision and medical costs. Type two represents interactions relates to service provision, where the main action of antibiotics use occurs. Several informal and formal interactions between physicians, pharmacists, patients and hospitals are subsumed under this rather broad category. Finally, type three embodies reciprocal interactions, 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 has interactions with scientific Non-Governmental Organizations (NGOs) or Islamic Republic of Iran Medical Council (IRIMC) or academia. Pharmaceutical companies have many formal and also informal interactions 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. For example, 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. As shown in figure 2, almost all interactions of circle 1 and circle 2 with circle 3 and circle 4, can be described as top-down governance-based relationships, while interactions between circle 1 and circle 2 can be described as a mixture of governance-based and reciprocal relationships. Circle 3 and circle 4 exhibit reciprocal interactions.
Many participants believed that interactions between key stakeholders in the antibiotics 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 the 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 regarding antibiotics. They argued that vital information circulated inefficiently and inadequately or with delay in the systems which adversely affect antibiotics use. For example, insurance companies produce antibiotics prescription information by analyzing physicians’ prescriptions, and send these information to IFDA or MOH, but there have been some logistic problems in IFDA recently that have impeded data transformation. The infrastructure of Information Technology in IFDA did not have enough capacity to integrate and process prescription-related information to be used effectively for policy making or providing feedbacks. Therefore the information on antibiotics use such as the percentage of prescriptions containing antibiotics is not updated to show a clear picture of current situation. Other important sources of antibiotics use data are hospitals and departments of the Food and Drug Administration in medical universities. They should report Rational Use of Drug (RUD) indicators such as the mean item per prescription and the percentage of prescriptions containing antibiotics MOH and IFDA, but they do not do it regularly and accurately. As a result MOH and IFDA do not have on time, accurate and detailed information of antibiotics prescription. In the absence of correct and updated information on antibiotics use, any planning and policy making to rationalize prescription and consumption would be challenging. Many patients participants in FGDs complained about the incomplete information about antibiotics use imparted to them by physicians and pharmacists. Physicians and pharmacists are supposed to educate their patients about antibiotics administration and use, but often they do not do that. This may consequently lead to irrational use of antibiotics, such as not completing treatment course and discontinue antibiotics use while they are recovering. Respondents working for research centers or scientific NGOs stated that despite their willingness to collaborate with IFDA or MOH to conduct some useful researches and participate in healthcare decision making, the stage had not been set for the smooth flow of necessary information.
Moreover, many participants criticized the quality and accuracy of information about antibiotics production and distribution run in the system. Pharmaceutical companies are supposed to send their data on medicine production and distribution to IFDA like the number of antibiotics distributed to pharmacies. However, distributing companies often send their information with delay and even the accuracy of the data is always seriously questioned. Based on the information provided by pharmaceutical distributing companies, IFDA should publish a report on official pharmaceutical statistics annually. As a result of delay in receiving the information which is questionable, this report usually is published with delay and its information is not reliable. Moreover, some interviewees argued that information circulation also happens through informal and non-documented channels, and so much of officially documented information exchange slips unnoticed. For example, through personal relationships between some employees in IFDA and pharmaceutical companies, the information on distributed antibiotics can transmitted timely but not through formal and official channels. However, this non-official information flow is temporary and lasts only as long as those people are in charge in IFDA.
Feedback loops
The main identified formal feedback mechanism in the system of antibiotics use in Iran is RUD indicators such as the mean item per prescription and the percentage of prescriptions containing antibiotics produced by insurance companies. 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. However, no systematic feedback mechanisms were identified from MOH, IFDA, or insurance companies to prescribers and other practitioners or vice versa in the system
There is some informal and even not easily observable feedback that forms the behavior of the system as follows:
Patients’ experience of antibiotic resistance which, increases the treatment failure of infectious diseases was found to negatively influence patients’ adherence to the treatment course, encouraging them to discontinue antibiotic therapy or consume more potent antibiotics. It was found to contribute to some physicians’ reluctance to adhere to medical guidelines, which can in turn increase irrational antibiotics prescription and perpetuate the vicious circle of antibiotic resistance.
Patients’ experience with previously used antibiotics may also 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 receive feedback about the success of their prescription from their patients by observing their symptoms. In addition, if patients are not satisfied with the dose or type of prescribed antibiotics, they may change their physicians or buy antibiotics from a pharmacy without prescription. The fear of losing patients, as doctors’ main source of income, for not prescribing antibiotics can sometimes override their willingness to adhere to medical guidelines and ethics, considering that there is direct financial relationships between patients and physicians in Iran. In addition, providing antibiotics over the counter worsens self-medication through increasing public access to antibiotics without prescription and encourages patients to buy more antibiotics as there is no significant negative feedback from authorities for selling antibiotics without prescription.
Rules and values
Different types of formal antibiotics related rules, regulations and guidelines were identified 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 were authorized by MOH and publicly accessible. However, it was identified that they were not always followed by the agents.
Interviewees who were clinical pharmacists argued that not all physicians easily adhered to evidence-based medicine or collaborate with clinical pharmacists to change their antibiotic prescriptions. Some defied pharmaceutical guidelines and dismiss them in favor of their own experiences. Clinical pharmacists believed that physicians’ different following rules behaviors may also be influenced by their prior interaction experience with pharmacists, and also health authorities.
Prescription and use of antibiotics behaviors were governed by the agents’ perception of formal rules, which could 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 internal official regulations and guidelines toward infectious disease, derived from formal regulations but 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 based on the internal context of hospitals or there should be a reasonable room for change and adaptation, which was not the case in their hospitals. However, the results of the study revealed that this self-organizational behavior of sub systems is 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 which could change overtimes as well. For example, insurance companies have clear and well-established credit and blame mechanisms that aim to restrict physicians’ over-prescription of antibiotics. Most participants agreed that rational use of antibiotics greatly matters also to governmental authorities due to the significance of antimicrobial resistance, which partly explains the establishment of Rational Use of Drugs committees in departments of Food and Drug Administration and hospitals. Likewise, among RUD indicators, the antibiotics use standard has always been an important indicator for MOH. However controversial it seems, 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 for failure of NCRUD in reducing irrational use of antibiotics was the lack of support of its organizational position by MOH. Although, the NCRUD is a national entity within the organizational structure of MOH, some reviewers believed that MOH does not delegate all RUD authority to it and support its enforcement.
In addition to organizational and professional values, individual values also influence the patients and physicians’ behavior concerning 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 healthcare managers. During some periods of time, 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 the antibiotics use system conducted by key agents, all influenced by their information, rules, values, resources, feedbacks and interaction with other agents.
Physicians’ prescription behaviors- 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. 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 exhibited different behaviors in public and private sectors. Additionally, some physicians argued that they were faced with time constraints in some settings and did 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 despite a long queue of patients.
Pharmaceutical companies and pharmacies behaviors- Data analysis of information provided by this study indicated that the behaviors of pharmaceutical companies and community pharmacies depended on many factors beyond their knowledge, the healthcare system or its rules. For example, their practices were 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 provided 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 behaviors of policy makers depended on their willingness to achieve short-term or long term outcomes, their personal preferences, characteristics and responsibility, contextual constraints, and experiences. One of the main reasons for tendency toward short term outcomes was identified as high speed policy makers’ turnover. Rather certain in the knowledge that they are not likely to hold to their coveted positions for too long, policymakers often set themselves short-term achievable goals, which will be touted as their legacies. Participants believed that the importance of irrational use of antibiotics varied among different managers and policy makers, reflected in their policies and programs. Variations could also be easily seen in preferences and perceptions among interviewees in policy making level. For example, some stated that rational use of antibiotics must strictly be rule-based, with others opposing and dismissing this view as unnecessarily harsh. In addition, some argued that resource constraints especially financial limitation usually put more pressures on policy makers to allocate required resources for programs aimed to improve rational use of antibiotics. Apart from personal preferences, it was also found that occasional crises, the context and limitations dictate certain behaviors and attitudes toward adherence to rules.
Patients’ antibiotics use behavior- Data analysis revealed that people’s antibiotics use behavior was 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, while, there is no need to antibiotics, some participants according to their individual experiences, believed in the efficacy of antibiotics, while others thought that their efficacy was not overweighed by their side effects.