[ETHICAL PERSPECTIVES AND DILEMMAS IN PRESCRIBING AND DISPENSING MEDICINAL PRODUCTS IN ISRAEL].

INTRODUCTION: Drug therapy is a central pillar in the provision of medical care. A significant number of doctor-patient encounters conclude with a prescription for a drug. These are subsequently followed by a pharmacist-patient interaction that ends with the dispensing of prescription drugs and/or a recommendation for an over-the-counter drug and other products. In Israel, the fields of medicine and pharmacy are highly regulated with extensive legislation.

Drug shortages in Israel, revisited: a bitter pill to swallow.

BACKGROUND: In 2017, we published an article addressing drug shortages (DS) in Israel, exploring regulatory perspectives, challenges, and potential solutions. Since then, DS remain a significant concern for patients, healthcare providers, and policymakers globally. In this updated article, we revisit the topic, providing new insights, data, and analysis on the current DS landscape in Israel, efforts to mitigate them, and propose strategies to combat this escalating issue. METHODS: We conducted a comprehensive search of the Israeli Ministry of Health (MOH) DS database, spanning from 2014 to the present. We extracted DS numbers and their reasons. Further searches on the Israeli MOH website, pharmaceutical division archives, and the internet yielded official MOH publications and correspondence regarding regulatory responses to DS from 2017 onwards. Additionally, two specific cases of DS were examined to analyze their handling. Recent activities and publications from the Israeli MOH aimed at reducing DS were also reviewed. RESULTS: Between 2014 and 2022, DS surged 2.66-fold. Total DS were 3228; 672 due to commercial reasons, and 2556 to operational reasons (20.5% and 79.5% respectively). The average duration of intermittent DS increased 1.56-fold, from 85 to 133 days. Manufacturers informed the MOH 22 days prior to actual shortage on average. Analyzing 2022's DS (640) by ATC groups, prominent categories included nervous system drugs (18%), drugs acting on the alimentary tract and metabolism (14%), and dermatologicals (11%). Operational DS in 2022 (n = 564) were primarily due to stock delivery delays (38%), stock over-utilization (12%), and raw material shortages (9%). Sixteen official MOH publications on DS were identified from 2017 onwards. Moreover, two high-impact DS case studies were examined. CONCLUSION: Despite routine monitoring by the Israeli MOH and updating the DS policy throughout this period, DS persist, intensifying annually and posing serious health risks. This trend mirrors international patterns, affecting countries globally. In Israel's uniquely structured healthcare system, with its swift stakeholder cooperation and implementation capabilities, more effective DS management is conceivable. We propose ten universally applicable rules to address DS challenges.

[Prescribing information for drugs--legal and regulatory implications].

The regulation of pharmaceuticals is becoming more complex in recent years. Current regulation is no longer limited to deciding whether a specific drug would be allowed to be placed on the market. Today, a significant part of the regulatory process is focused on setting the terms for utilization of each drug, regarding the target population, dosages, mode of administration, etc. These terms have enormous implications on both pharmaceutical companies and caregivers. In Israel, the only publicly available source of information on terms of registration is the prescribing information ("physician leaflet"). The prescribing information contains instructions for use, as well as a Lot of safety information regarding the product. Therefore, the wording of the prescribing information may have serious regulatory and legal implications on caregivers. The objective of this article is to describe the relevant laws and regulations requiring its publication, while discussing the practical issues and implications of the use of prescribing information by physicians in Israel.

Legal and regulatory aspects of orphan drugs.

Rare (orphan) diseases are defined as diseases whose prevalence is significantly low. Many of these diseases are diagnosed at childhood by pediatricians. Rare diseases pose many obstacles for health care systems in general and patients specifically. As they are rare, they are less investigated, there is less knowledge about the disease and less professionals specializing in it. Furthermore, as for most diseases there is no specific treatment, diagnosis is not relevant. From industry perspective, as the market potential is small, there is no financial incentive to invest in developing treatments for rare diseases. All the above led patients, researchers and policymakers around the world to legislate specific laws designated to encourage and provide incentives for researchers and for the pharmaceutical industry to develop scientific and clinical knowledge as well as potential treatments for these diseases. The objective of this article is to describe the initiation and current status of public health policy concerning orphan disease and drugs.

[The influence of the relationship between physicians and pharmaceutical companies on the patient from the point of view of policy-makers in Israel].

BACKGROUND: The relationship between doctors and pharmaceutical companies is an integral part of the health system in Israel and the whole world. The mutual need for such a relationship requires us, as a society, to examine its influence on the individual and the system as a whole. AIM: This research examines the relationship from the points of view of the relevant parties within the health system and outside the health system (decision-makers). METHODS: The authors used in-depth interviews and qualitative research methods in order to examine and understand the various positions of decision-makers. FINDINGS AND CONCLUSION: The position of the decision-makers, regarding all the aspects of this relationship, expresses their wishes and depends on their point of view. The impact of the relationship between the doctors and the pharmaceutical companies was examined with regard to the prescription behavior of the doctor. All the government representatives, all the physicians' representatives and those of the health funds, believe that the physicians' prescription behavior is impacted by the relationship. There are those who perceive this to be a negative trend and some doctors believe it to be a positive trend. With regard to possible harm to the patient, the parties believe that the relationship does not harm the patient, whereas most of the government representatives identify harm to the patients, both on the economic and health levels. The authors believe that the "influence" which exists or could exist on the part of the pharmaceutical companies is the main stumbling block in this relationship, which is expressed in the decision-makers' perspective.

[Legal and regulatory aspects of physicians' prescriptions].

The prescribing authority is one of the powers granted solely to physicians, as part of their professional definition in the Israeli law. Prescribing is one of the most common activities in the daily work of the physician. It is estimated that on average every physician in Israel writes more than a thousand prescriptions annually. In this situation, where prescribing is a formal-legal activity, one expects that this issue should be defined clearly by law. However, a review of the relevant Israeli laws and regulations reveals that many questions regarding prescribing and prescriptions are not dealt with by the law, and that most physicians are not familiar with it. Therefore, the objective of this article is to highlight the legal issues arising from the legislation regarding prescribing versus the prevailing practices of physicians. Since this issue is very complex, we divided the article into two parts the first part deals with legal and regulatory aspects of prescribing, while the second part deals with unique prescriptions, including financial aspects of hospitals and Sick Funds prescriptions, narcotic prescriptions and prescriptions for non-approved drugs.

Registration of pharmaceuticals in Israel and its exemptions.

The requirement to obtain a preliminary approval for every pharmaceutical product in order to allow its regular distribution is an accepted practice worldwide. In Israel, the preliminary approval is known as registration in the national drug registry. The mechanism of drug registration has been in place since 1964, and is now based on Article 47A(b) of the Pharmacists Ordinance [New Version], 1981. The procedure of pharmaceutical registration is designed to assure that all pharmaceuticals marketed in Israel would prove to be safe, efficacious and of proper quality. However, in certain cases, it may lead to prevention of the distribution of necessary products that could not be registered for various reasons. In the context of pharmaceuticals, the unavailability of certain products may leave patients without proper treatment and put them in serious danger. This problem requires the duty of registration to have some exemptions. These exemptions must be balanced between the desire to assure a high level of preliminary evaluation of pharmaceutical products on the one hand, and the healthcare system's need to use products which have not been fully examined, on the other hand. This article analyzes the Israeli model of the exemptions from the duty to register drugs.

[E-commerce of pharmaceuticals].

The emergence of the Internet as a new communications and information technology caused major social and cultural changes. The dramatic increase in accessibility and availability of information empowered the consumer by closing the information gap between the consumer and different suppliers. The objective of this article is to review many new internet-supported applications related to the pharmaceutical market. E-commerce is divided into two major components: Business to Consumer (B to C), and Business to Business (B to B). The main applications in B to C are dissemination of medical and drug information, and the sale of drugs through the Internet. Medical information on the Internet is vast and very helpful for patients, however, its reliability is not guaranteed. Online pharmacies increase the accessibility and availability of drugs. Nevertheless, several obstacles such as security of the data provided (both financial and clinical) prevent the widespread use of online pharmacies. Another risk is the health authorities' inability to regulate Internet sites effectively. Therefore, unregulated sale of prescription drugs, fake or substandard, often occurs on the Internet. B to B relates to physicians, clinics, hospitals, HMO's and pharmaceutical companies. There is a vast number of applications ranging from clinical research, marketing and sales promotion, to drug distribution and logistics. In conclusion, the Internet is dynamic and has contributed to the development of numerous new applications in the field of pharmaceuticals. Regulatory authorities should be active in developing new policies that will deal with those new Internet-based applications.

[Evaluation of the impact of a clinical pharmacist on the quality and cost of pharmacotherapy in a general surgical department, the Hillel-Yaffe Medical Center].

BACKGROUND: Clinical pharmacy could be defined as an umbrella of services aimed at maximizing the pharmacotherapeutic effect, minimizing the risk for developing adverse drug effects and reducing drug expenditures for the health care system. Clinical pharmacists, in Israel and abroad, have been practicing in different health care settings aiming to implement the principles mentioned above. Most of the articles previously published reviewed the role of the clinical pharmacist in internal medicine wards or in intensive care units. This article focuses on the role of the clinical pharmacist in a general surgery department and the influence of this service on the quality and cost of pharmacotherapy and on intravenous antibiotic therapy in particular. AIMS: Improving the quality of pharmacotherapy while optimally using economic resources in a general surgery ward. METHODS: During September 1999 to August 2000, the clinical pharmacist joined physician rounds in the surgical ward. During the rounds he advised physicians about clinical and economical aspects of drug treatment, and collected data on his activity on a specific designated form. The data was processed on a central computerized database, and analyzed to determine the influence of the clinical pharmacist on clinical and economical outcomes. RESULTS: At the end of the study period the following were found: The pharmacist made 219 interventions. These included adverse drug effects, which were identified and/or prevented. When considering the economic data, a substantial reduction of 56% in intravenous antibiotic therapy was noted (direct saving of about 140,000 NIS). Such savings were accompanied by changes in the prescribing patterns in the department, which were translated into increased rate of oral antibiotic prescribing and reduction in the use of certain i.v. antibiotics while undamaging the quality of the pharmacotherapeutic effect. CONCLUSION: The results of this study indicate that participation of a clinical pharmacist during physicians rounds improved the quality of the pharmacotherapy, assisted in changing clinicians prescribing habits, and at the same time significantly reduced the direct expenditures on medications in general and of intravenous antibiotic therapy in particular.