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Digital technologies to improve effectiveness of pharmacotherapy
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International Conference on Knowledge Based and Intelligent Information and Engineering Systems, KES2018, 3-5 September Belgrade, Serbia and Engineering International Conference on Knowledge Based and 2018, Intelligent Information Systems, KES2018, 3-5 September 2018, Belgrade, Serbia
Digital technologies to improve effectiveness of pharmacotherapy Digital technologies to improve effectiveness of pharmacotherapy Koshechkin K.A.a,c*, Polikarpov A.V. b,c, Radzievsky G.P.c Koshechkin K.A.a,c*, Polikarpov A.V. b,c, Radzievsky G.P.c a Federal State Budgetary Institution Scientific Centre for Expert Evaluation of Medicinal Products of the Ministry of Health of the Russian
Federation, 8/2 Petrovsky boulevard, Moscow 127051, Russia Federal State Budgetary Institution Scientific Centre for Expert Evaluation of Medicinal Products of the Ministry of Health of the Russian Federal Research Institute for Health Organization and Informatics of Ministry of Health of the Russian Federation, 11, Dobrolubov str., Federation, 8/2 Petrovsky boulevard, Moscow 127051, Russia Moscow, 127254, Russia b Federal Research Institute for Health Organization and Informatics of Ministry of Health of the Russian Federation, 11, Dobrolubov str., c Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Moscow, 127254, Russia Health of the Russian Federation (Sechenov University) 2-4 Bolshaya Pirogovskaya st., Moscow 119991, Russia c Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University) 2-4 Bolshaya Pirogovskaya st., Moscow 119991, Russia a b
Abstract Abstract Medical drugs interactions and adverse drug reactions are one of the major problems in pharmacotherapy. At the Sechenov University (Russia, Moscow), digital system for drug prescription management is being developed. Artificial intelligence Medical drugs interactions and adverse drug reactions are one of the major problems in pharmacotherapy. At the Sechenov methods to(Russia, the control of drug digital therapysystem will greatly enhance the ability of the automated system to identify potential University Moscow), for drug prescription management is being control developed. Artificial intelligence problems in drug therapy and provide recommendations for their elimination. Introduction of this system into commercial methods to the control of drug therapy will greatly enhance the ability of the automated control system to identify potential operation will make it possible to translate the civil circulation of medicines into a single information space and increase the problems in drug therapy and provide recommendations for their elimination. Introduction of this system into commercial effectiveness the ongoing pharmacotherapy. operation willofmake it possible to translate the civil circulation of medicines into a single information space and increase the © 2018 The Authors. Published by Elsevier B.V. effectiveness of the ongoing pharmacotherapy. © 2018 The Authors. Published Ltd. Peer-review under responsibilityby ofElsevier KES International. © 2018 The Authors. by Elsevier B.V. This is an open accessPublished article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/) Peer-review under responsibility of KES International. Selection and peer-review under responsibility of KES International. Keywords: medical information system; electronic health record; medicinal products circulation; artificial intelligence methods; pharmacology; pharmacogenetics; personalized medicine Keywords: medical information system; electronic health record; medicinal products circulation; artificial intelligence methods; pharmacology; pharmacogenetics; personalized medicine
1. Main text 1. Main text 1.1 Introduction 1.1 Introduction Currently, in Russian Federation and worldwide pharmacy business is being actively restructured through the introduction Significant progress in medical pharmacological knowledge and the Currently, of in digital Russiantechnologies. Federation and worldwide pharmacy business and is being actively restructured through the emergence of a large number of complex and effective medicines lead to an increasing role of drug control introduction of digital technologies. Significant progress in medical and pharmacological knowledge and and the constantly task of andeffective nurses inmedicines maintaining proper theofmedicines they and use emergence complicate of a large the number of physicians complex and lead to anknowledge increasing of role drug control to treat patients. Recently, some public health specialists have begun to raise the issue of extending the professional constantly complicate the task of physicians and nurses in maintaining proper knowledge of the medicines they use responsibilities pharmacists due to increased responsibility patient treatment and the process ofthe using drugs. to treat patients.ofRecently, some public health specialists havefor begun to raise the issue of extending professional responsibilities of pharmacists due to increased responsibility for patient treatment and the process of using drugs. * Corresponding author. E-mail address: [email protected] * Corresponding author. E-mail address: [email protected] 1877-0509 ã 2018 The Authors. Published by Elsevier B.V. Peer-review under responsibility of KES International 1877-0509 ã 2018 The Authors. Published by Elsevier B.V. Peer-review under responsibility of KES International 1877-0509 © 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/) Selection and peer-review under responsibility of KES International. 10.1016/j.procs.2018.08.080
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Changes in the financing and organization of health care require healthcare institutions, including pharmacies, to reduce costs while maintaining high quality of patient care. The accompanying implementation of digital systems that perform many of the data processing and recordkeeping functions that pharmacists load will accelerate the shift in the activity of pharmacists from the control of the release of medical products to the control of individual drug use. One of the most important problems of the healthcare system in the face of the constantly growing costs of medicines, medical products and medical equipment is to ensure the availability of medical care provided to the population of the Russian Federation. The solution to this problem is the creation of a digital system for increasing the effectiveness of pharmacotherapy. The use of a digital assistant allows to stimulate the use of the most clinically effective and safe medical technologies with the best cost-effectiveness ratio, contributes to the following tasks: rational allocation of resources in the healthcare system and increase of the effectiveness of their use; improvement of clinical practices; reimbursement of the cost of medicines, medical equipment and interventions; rational pricing for medical technology; the promotion of innovative medical technologies. Potentially dangerous combinations of drugs are a serious clinical, social and economic problem of the health system and the state as a whole. Eventually lots of medicines prescribed by doctors are potentially dangerous. Although few percent of patients receiving potentially dangerous combinations of drugs develop unwanted reactions. According to statistics, 128,000 patients die every year from unwanted reactions in the US only. The cause of death is 1/3 of them - interactions of drugs associated with the use of potentially dangerous combinations [1]. In addition, the costs of treating unwanted reactions arising from the use of potentially dangerous combinations are half the costs of treating all drug complications. Existing domestic and foreign digital assessment systems allow us to predict the interaction of only two drugs. In practical medicine, especially in geriatrics, the number of drugs used at the same time usually exceeds 3. Also, the risk of side effects with incompatibilities of drugs increases in proportion to the number of drugs used simultaneously. In this regard, the development of an expert system based on the latest achievements of personalized medicine and predicting the dangerous interactions of 3 or more drugs is an important social, clinical and economic goal of public health. In the current system of preferential drug provision, the funds allocated for these purposes are not always used effectively. Absence of the system of drug insurance of patients makes it practically impossible to receive medical assistance without state support in the treatment of a number of diseases. A solution to this problem may include, among other things, the introduction of a system for providing medicines by taking into account the principles of drug insurance for the population of the Russian Federation. 1.2 Body One of the main problems of the organizations and institutions engaged in the turnover of medicines is the methodology for the common key performance indicators for pharmaceutical treatment evaluation. The overwhelming majority of medical organizations do not have mechanisms for intellectual analysis of the nomenclature of the consolidated planned need in medicines for: • compliance with current records of the State Register of Medicines; • absence of counterfeit and counterfeit medicines in the list; • frequency of occurrence in standards of medical care, clinical recommendations, integrated electronic medical records of patients; • availability of cheaper counterparts with comparable efficiency. The evaluation of the optimal turnover of medicines ensures, on the one hand, rational prescribing of medicines taking into account the needs of personalized, translational and regenerative medicine based on the application of medical care standards and clinical recommendations, and on the other hand, ensures the rational distribution of financial resources related to the purchase and storage of medicinal products. At the same time, the quality of
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medical care is improved through clinically effective drug therapy based on evidence-based methods, and rational use of financial resources of the health care system for patient treatment. Effective use of drugs, both clinically and economically, is impossible without a serious automation of processes based on the use of digital systems, knowledge bases and mathematical methods of choice of solutions [2,3]. At the present time, various digital systems are being intensively introduced, both in the automation of financial and economic activities and in the therapeutic process. To the automation systems of financial and economic activities in terms of turnover of medicines are the management systems of pharmacy organizations, including services for collecting applications from treatment departments, procurement management, distribution of drugs and management of write-offs. At automation of medical process digital systems providing rational distribution of medical products, control of their application and an estimation of results of their use [4]. At the Sechenov University (Russia, Moscow), the optimal organizational, information and mathematical model of drug turnover management is being developed, based on formalized knowledge and mathematical methods of decision-making. The main practical task of the project is the development of an information system that provides optimal control over the turnover of medicines that implements the developed theoretical solutions. Obviously, the expenditure of financial resources for medicines must be strictly controlled. The mechanisms of this control (in the implementation of the principles of drug insurance) can be different: a positive list (the list of permitted medicines) is the most effective method of not only control but also management - the positive list should include only medicines, the effectiveness of which is confirmed in terms of Evidence medicine, moreover, at predetermined prices. Nowadays such a system is being developed on federal level with a goal to determine less expansive medicines in a common group of preparations with equal composition of active substances and routs of administration [5]. The negative list are medicines that are not refundable. Thus, the costs of branded and / or innovative drugs may not be reimbursed in the presence of similar generics (with proven clinical efficacy). Often a negative list is also used to stimulate the development of the domestic pharmaceutical industry by prohibiting reimbursement of expenses for some imported drugs. Equally important is the issue of prices for medicines, which are reimbursed under insurance programs. Another mechanism that effectively regulates the consumption of medicines reimbursed under insurance programs in some countries is the joint payment of medicines. The size and type of co-payment may vary depending on the type of medication, disease, age and many other factors. According to the existing trends, the transition to drug insurance is possible in the coming years. Creation of mathematical models of insurance based on the analysis of factors explaining the use of medicines is an important task of insurance medicine and improving the quality of drug assistance and the effectiveness of the health care system. The scale of the tasks put forward for the informatization of public health requires the joint efforts of the state and business within the framework of public-private partnership with the aim of increasing the efficiency, safety and accessibility of medical services and medicines for the population of the Russian Federation. According to modern estimates, with the introduction of an automated system for the registration of medicines, it is possible to save 10% on medicine costs, which is relevant throughout the country. However, this cannot be achieved without solving a large and complex problem - the integration of databases, knowledge bases and elements of applied systems (electronic medical cards, digital medical equipment, mobile clients, disk libraries, data servers, broadband networks, etc.). Also, the proposed approach will unite and strengthen the aggregate potential of leading experts by integrating it into a single knowledge base, as well as using a set of modern methods for extracting, analyzing and forecasting them based on semantically oriented technologies in the field of large data (classification, clustering, neural networks, training, etc.). The system architecture will simultaneously provide a number of important operational qualities, such as: reliability, availability, security, fault tolerance, mobility and ergonomics. The system will also be used to calculate individual regimens of patients taking medications, including those with a narrow therapeutic range (small difference between the minimum effective dose and the maximum non-toxic dose, and also the choice of solution composition for patients receiving all their fluid and nutrition through intravenous infusions). It is known that the level of drug concentration in the blood increases when the ingested medicine is
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absorbed in the body, and then falls when the drug spreads through other tissues, then biotransformed and removed from the body. For drugs with a narrow therapeutic range (with little difference between the minimum effective and maximum safe concentration), the dose intervals and single dose should be carefully calculated to ensure drug concentration in a given range. Too little concentration will not give the desired therapeutic effect, too high will lead to side effects and, in some cases, death. The researchers developed pharmacokinetic models that represent the level of the drug in the blood as a function of the number of doses of the drug and the time they are taken, the way the medication is administered; specific pharmacokinetic parameters of the drug (e.g. duration of drug withdrawal from the body and removal from the body tissues); (for example, age, sex, and ideal body weight), as well as concomitant therapy and disease factors that affect the effects of the drug (e.g., coronary insufficiency, pneumonia, smoking, and concomitant use of phenobarbital are among the factors that affect the effect of theophylline - bronchodilator, used to treat bronchospasm spasm in bronchial asthma and pulmonary emphysema). Medical professionals use pharmacokinetic models to predict the future level of drug concentration in the blood and thus to determine the optimal regimens for therapy. Since the 1970s, Jeliff and colleagues have presented one of the first systems to assist physicians in determining dosage regimens in the use of digitalis, then described the Bayesian predictive model in which parameters of the pharmacokinetic model varied depending on the results of laboratory serum drug concentrations [6]. This model was tuned to a particular patient and thus provided a better match between the measured and predicted drug concentrations. Currently, there are computer programs that provide rapid calculation of drug concentrations using complex pharmacokinetic equations; these calculations help clinicians predict the effectiveness of drug therapy and strengthen the role of clinical pharmacotherapists in conducting pharmacokinetic consultations. Also, digital systems have been used to formulate solutions intended for intravenous infusion to patients who are thus partially or completely fed. When preparing such solutions, physicians and pharmacists must take into account a large number of factors, singly and in combination. These factors include the patient's fluid balance and calorie content, the level of dextrose (sugar) and lipid (fat) content, as well as the electrolytic balance (potassium, sodium, calcium, etc.). The preparation of nutrient solutions is particularly difficult in the treatment of newborns and other pediatric patients, since for them the mineral composition and caloric content of solutions should be high, but the volume of fluid consumed must be severely limited. Without the help of a computer, doctors and pharmacists have to manually calculate and verify recipes that must satisfy many limitations. The developed system will be able to perform many of the pharmacy functions for the dispensing and distribution of medicines. Already, there are technologies for automating most of the process of using drugs from the moment of making a therapeutic decision to taking the medicine by the patient; with its help it will be possible to use computers for routine monitoring of prescriptions to identify potential adverse reactions, to draw the attention of pharmacists to complicated or unusual appointments, as well as for automatic packaging of tablets and capsules by sachets for dispatch to the patient. The use of barcodes in pharmacies can eliminate the last significant technological obstacle for the dispensing of drugs using computer-controlled automata. Used in all supermarkets, bar-code technology is already used in a number of hospitals for marking blood samples, case histories, envelopes with X-rays. Pharmacy robots are already used in Japan, and in the US their prototypes are being tested. Another potential application of bar code technology in pharmacies is the automatic control of the stock of medical goods and computerized control over the shelf life of medicines and the write-off of overdue medical products. The use of barcodes can even reduce the number of errors in taking medications - medical professionals will be able to verify that the given medicine is correctly given to exactly this patient by scanning the patient's identification bracelet with the bar code printed on it and the label with the bar code on the medicine package. The Ministry of Health of the Russian Federation has prepared a Concept for the creation of a federal state information system for monitoring the movement of medicinal products from the manufacturer to the end consumer using labeling. Particular attention is paid to interaction with external information systems, which allows for integration with the digital system to improve the effectiveness of pharmacotherapy. The structure of external systems that carry out information interaction with components includes: information systems of federal executive bodies of the Russian Federation; information systems of manufacturers of medicines; information systems of organizations engaged in wholesale trade in medicinal products; information systems of pharmacy organizations;
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information systems of medical organizations; information systems of organizations engaged in the destruction of medicinal products. The technology of local networks and telecommunications implemented in the system also affect the pharmacy business. Automating the process of registering recipes will not only speed up their filling, but will provide an opportunity for immediate feedback from doctors to provide them with information about the effectiveness and consistency of their appointments. For example, if a doctor enters a prescription for a medicine and the computer identifies a potential drug interaction, then this information will be provided to him immediately, and not several hours later - and maybe too late. In addition, pharmacists will no longer be chained to local databases and will have quick access to national databases containing information on the prices of medicines, medicines, the use of which is paid by specific payers of medical services, as well as the criteria for optimizing the use of medicines. The system will perform processing requirements in real time, while checking the presence of potential problems in prescriptions, for example, drug interactions. Pharmacies will be able to directly connect to this system via the Internet, which will allow them to receive an immediate decision regarding the recipes they provide. This same digital technology will promote the growth of opportunities for professional communication with pharmacy computer systems. Any state pharmacist can become a participant in such a conference. The system will allow users to sign up for participation in a number of thematic teleconferences and take part in them, by contacting the university system via dial-up telephone lines. Working on their personal computer, participants will be able to view the lists of issues discussed within the framework of this thematic teleconference and send their comments to the system. Implementing systems at the treatment site, using bedside terminals to collect critical information, such as symptoms and medication data, will increase the medical component of the databases and allow for the implementation of fairly sophisticated individual drug control methods. For example, it will be possible to establish exactly which medication the patient has taken and when it happened. Detailed and accurate information about medications and symptom information are essential for evaluating therapeutic regimens, controlling the effectiveness of drug therapy, and detecting adverse drug reactions. At the present time, it became possible not only to represent any kind of information - numbers, texts, sound, images - in a digital format suitable for storage and processing in a personal computer, but also an infrastructure for its high-speed distribution. As an example, an LTE network (the standard for wireless high-speed data transmission for mobile phones and other data terminals) is present in 83 regions of Russia, and 70% of the population in the coverage zone (as of the beginning of 2016) [7]. These technologies provide an opportunity to provide instant access to a huge range of information systems using personal pocket computers, the functionality of which contains most modern mobile phones. The system will allow the implementation of mobile devices for optimization in drug provision of the population. It includes distance trade in medicines, support for the selection of pharmacotherapy methods, electronic prescriptions and appointments, electronic records in the medical history, electronic document management associated with this direction, as well as warehouse accounting systems. Rapid access to detailed clinical data and application of artificial intelligence methods to the control of drug therapy will greatly enhance the ability of the automated control system to identify potential problems in drug therapy and provide recommendations for their elimination. In addition, the continued development of pharmacological knowledge bases will have a major impact on the reform of pharmaceutical information services. Integration of such knowledge bases and automated hospital information systems will provide pharmacy workers and other medical personnel with operational access to actual information about medicines. Medical specialists will be able to receive from clinical consultation systems and expert advice on the planning of therapy. In the course of project implementation, an information system for the optimal management of medicines and medical technologies in medical organizations will be created based on the application of clinical recommendations. The system will consist of two main blocks: a knowledge base that is unified for all medical organizations, accompanied by a single scientific and methodological center and an information system for managing the turnover of medicines, integrated with other information systems, components of the Unified State Health Information System (as shown on figure 1) operating on the basis of a single knowledge base.
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Fig. 1. Unified
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State Health Information System and Digital pharmacotherapy improvement system integration scheme.
The knowledge base will be a repository of formalized knowledge, including a semantic network of medicines, algorithms and mathematical methods for processing knowledge and decision-making, methods of automated learning and the formation of rules for the derivation of solutions. Knowledge base management will be provided by an information system that provides expert work, interaction with various sources of knowledge and data, normative and reference information. The commercialization of the project is achieved through the sale of information systems for the management of drugs, in the future also through subscriber access to the knowledge base from other applications. 1.3 Conclusion Thus, the introduction of this system into commercial operation will make it possible to translate the civil circulation of medicines into a single information space and increase the effectiveness of the ongoing pharmacotherapy, and as a result, to improve the key indicators of public health. It can be confidently asserted that the list of digital solutions of such a scale ready for implementation in the organizations of the sphere of circulation of medicines is currently quite small. This creates a great growth potential, which can be realized in the shortest possible time and without significant financial costs for competition. And as a result it is a promising opportunity to increase of the effectiveness of pharmacotherapy and public health in general.
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References 1. Donald W. Light New Prescription Drugs: A Major Health Risk With Few Offsetting Advantages. Edmond J. Safra Center for Ethics Harvard University https://ethics.harvard.edu/blog/new-prescription-drugs-major-health-risk-few-offsetting-advantages 2. Lipaev V. V., Potapov AI Estimation of expenses for the development of software. - Moscow: Finances and Statistics, 1988. - 156 p. 3. Bunova EV, Buslaeva O.S. Evaluation of the effectiveness of the introduction of information systems // Bulletin of the Astrakhan State Technical University. Series: Management, Computing and Informatics, Issue 1, 2012. 4. G.Lebedev, Y.Tikhonova. Information system for pharmacotherapy method selection // International Conference on Knowledge Based and Intelligent Information and Engineering Systems, KES2017, 6-8 September 2017, Marseille, France / Procedia Computer Science. Vol.112, 2017, Pages 1658-1663. 5. A.A. Svistunov, Yu.V. Olefir, G.S. Lebedev, K.A. Koshechkin Formation of a single information space in the sphere of medicinal products circulation // Pharmateka Special issue Otorhinolaryngology 2017, p. 51-55. 6. Jelliffe, R. et al. Achieving target goals most accurately using nonparametric compartmental models and "multiple model" design of dosage regimens. Ther. Drug. Monit., V. 22, p. 346-353, 2000 7. A.A. Svistunov, Yu.V. Olefir, G.S. Lebedev, K.A. Koshechkin Telemedicine. The next stage is telepharmacy? // Electronic scientific publication (scientific and practical journal) "Social aspects of public health" N4 2017 http://vestnik.mednet.ru/content/view/849/27/lang,ru/
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International Conference on Knowledge Based and Intelligent Information and Engineering Systems, KES2018, 3-5 September Belgrade, Serbia and Engineering International Conference on Knowledge Based and 2018, Intelligent Information Systems, KES2018, 3-5 September 2018, Belgrade, Serbia
Digital technologies to improve effectiveness of pharmacotherapy Digital technologies to improve effectiveness of pharmacotherapy Koshechkin K.A.a,c*, Polikarpov A.V. b,c, Radzievsky G.P.c Koshechkin K.A.a,c*, Polikarpov A.V. b,c, Radzievsky G.P.c a Federal State Budgetary Institution Scientific Centre for Expert Evaluation of Medicinal Products of the Ministry of Health of the Russian
Federation, 8/2 Petrovsky boulevard, Moscow 127051, Russia Federal State Budgetary Institution Scientific Centre for Expert Evaluation of Medicinal Products of the Ministry of Health of the Russian Federal Research Institute for Health Organization and Informatics of Ministry of Health of the Russian Federation, 11, Dobrolubov str., Federation, 8/2 Petrovsky boulevard, Moscow 127051, Russia Moscow, 127254, Russia b Federal Research Institute for Health Organization and Informatics of Ministry of Health of the Russian Federation, 11, Dobrolubov str., c Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Moscow, 127254, Russia Health of the Russian Federation (Sechenov University) 2-4 Bolshaya Pirogovskaya st., Moscow 119991, Russia c Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University) 2-4 Bolshaya Pirogovskaya st., Moscow 119991, Russia a b
Abstract Abstract Medical drugs interactions and adverse drug reactions are one of the major problems in pharmacotherapy. At the Sechenov University (Russia, Moscow), digital system for drug prescription management is being developed. Artificial intelligence Medical drugs interactions and adverse drug reactions are one of the major problems in pharmacotherapy. At the Sechenov methods to(Russia, the control of drug digital therapysystem will greatly enhance the ability of the automated system to identify potential University Moscow), for drug prescription management is being control developed. Artificial intelligence problems in drug therapy and provide recommendations for their elimination. Introduction of this system into commercial methods to the control of drug therapy will greatly enhance the ability of the automated control system to identify potential operation will make it possible to translate the civil circulation of medicines into a single information space and increase the problems in drug therapy and provide recommendations for their elimination. Introduction of this system into commercial effectiveness the ongoing pharmacotherapy. operation willofmake it possible to translate the civil circulation of medicines into a single information space and increase the © 2018 The Authors. Published by Elsevier B.V. effectiveness of the ongoing pharmacotherapy. © 2018 The Authors. Published Ltd. Peer-review under responsibilityby ofElsevier KES International. © 2018 The Authors. by Elsevier B.V. This is an open accessPublished article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/) Peer-review under responsibility of KES International. Selection and peer-review under responsibility of KES International. Keywords: medical information system; electronic health record; medicinal products circulation; artificial intelligence methods; pharmacology; pharmacogenetics; personalized medicine Keywords: medical information system; electronic health record; medicinal products circulation; artificial intelligence methods; pharmacology; pharmacogenetics; personalized medicine
1. Main text 1. Main text 1.1 Introduction 1.1 Introduction Currently, in Russian Federation and worldwide pharmacy business is being actively restructured through the introduction Significant progress in medical pharmacological knowledge and the Currently, of in digital Russiantechnologies. Federation and worldwide pharmacy business and is being actively restructured through the emergence of a large number of complex and effective medicines lead to an increasing role of drug control introduction of digital technologies. Significant progress in medical and pharmacological knowledge and and the constantly task of andeffective nurses inmedicines maintaining proper theofmedicines they and use emergence complicate of a large the number of physicians complex and lead to anknowledge increasing of role drug control to treat patients. Recently, some public health specialists have begun to raise the issue of extending the professional constantly complicate the task of physicians and nurses in maintaining proper knowledge of the medicines they use responsibilities pharmacists due to increased responsibility patient treatment and the process ofthe using drugs. to treat patients.ofRecently, some public health specialists havefor begun to raise the issue of extending professional responsibilities of pharmacists due to increased responsibility for patient treatment and the process of using drugs. * Corresponding author. E-mail address: [email protected] * Corresponding author. E-mail address: [email protected] 1877-0509 ã 2018 The Authors. Published by Elsevier B.V. Peer-review under responsibility of KES International 1877-0509 ã 2018 The Authors. Published by Elsevier B.V. Peer-review under responsibility of KES International 1877-0509 © 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/) Selection and peer-review under responsibility of KES International. 10.1016/j.procs.2018.08.080
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Changes in the financing and organization of health care require healthcare institutions, including pharmacies, to reduce costs while maintaining high quality of patient care. The accompanying implementation of digital systems that perform many of the data processing and recordkeeping functions that pharmacists load will accelerate the shift in the activity of pharmacists from the control of the release of medical products to the control of individual drug use. One of the most important problems of the healthcare system in the face of the constantly growing costs of medicines, medical products and medical equipment is to ensure the availability of medical care provided to the population of the Russian Federation. The solution to this problem is the creation of a digital system for increasing the effectiveness of pharmacotherapy. The use of a digital assistant allows to stimulate the use of the most clinically effective and safe medical technologies with the best cost-effectiveness ratio, contributes to the following tasks: rational allocation of resources in the healthcare system and increase of the effectiveness of their use; improvement of clinical practices; reimbursement of the cost of medicines, medical equipment and interventions; rational pricing for medical technology; the promotion of innovative medical technologies. Potentially dangerous combinations of drugs are a serious clinical, social and economic problem of the health system and the state as a whole. Eventually lots of medicines prescribed by doctors are potentially dangerous. Although few percent of patients receiving potentially dangerous combinations of drugs develop unwanted reactions. According to statistics, 128,000 patients die every year from unwanted reactions in the US only. The cause of death is 1/3 of them - interactions of drugs associated with the use of potentially dangerous combinations [1]. In addition, the costs of treating unwanted reactions arising from the use of potentially dangerous combinations are half the costs of treating all drug complications. Existing domestic and foreign digital assessment systems allow us to predict the interaction of only two drugs. In practical medicine, especially in geriatrics, the number of drugs used at the same time usually exceeds 3. Also, the risk of side effects with incompatibilities of drugs increases in proportion to the number of drugs used simultaneously. In this regard, the development of an expert system based on the latest achievements of personalized medicine and predicting the dangerous interactions of 3 or more drugs is an important social, clinical and economic goal of public health. In the current system of preferential drug provision, the funds allocated for these purposes are not always used effectively. Absence of the system of drug insurance of patients makes it practically impossible to receive medical assistance without state support in the treatment of a number of diseases. A solution to this problem may include, among other things, the introduction of a system for providing medicines by taking into account the principles of drug insurance for the population of the Russian Federation. 1.2 Body One of the main problems of the organizations and institutions engaged in the turnover of medicines is the methodology for the common key performance indicators for pharmaceutical treatment evaluation. The overwhelming majority of medical organizations do not have mechanisms for intellectual analysis of the nomenclature of the consolidated planned need in medicines for: • compliance with current records of the State Register of Medicines; • absence of counterfeit and counterfeit medicines in the list; • frequency of occurrence in standards of medical care, clinical recommendations, integrated electronic medical records of patients; • availability of cheaper counterparts with comparable efficiency. The evaluation of the optimal turnover of medicines ensures, on the one hand, rational prescribing of medicines taking into account the needs of personalized, translational and regenerative medicine based on the application of medical care standards and clinical recommendations, and on the other hand, ensures the rational distribution of financial resources related to the purchase and storage of medicinal products. At the same time, the quality of
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medical care is improved through clinically effective drug therapy based on evidence-based methods, and rational use of financial resources of the health care system for patient treatment. Effective use of drugs, both clinically and economically, is impossible without a serious automation of processes based on the use of digital systems, knowledge bases and mathematical methods of choice of solutions [2,3]. At the present time, various digital systems are being intensively introduced, both in the automation of financial and economic activities and in the therapeutic process. To the automation systems of financial and economic activities in terms of turnover of medicines are the management systems of pharmacy organizations, including services for collecting applications from treatment departments, procurement management, distribution of drugs and management of write-offs. At automation of medical process digital systems providing rational distribution of medical products, control of their application and an estimation of results of their use [4]. At the Sechenov University (Russia, Moscow), the optimal organizational, information and mathematical model of drug turnover management is being developed, based on formalized knowledge and mathematical methods of decision-making. The main practical task of the project is the development of an information system that provides optimal control over the turnover of medicines that implements the developed theoretical solutions. Obviously, the expenditure of financial resources for medicines must be strictly controlled. The mechanisms of this control (in the implementation of the principles of drug insurance) can be different: a positive list (the list of permitted medicines) is the most effective method of not only control but also management - the positive list should include only medicines, the effectiveness of which is confirmed in terms of Evidence medicine, moreover, at predetermined prices. Nowadays such a system is being developed on federal level with a goal to determine less expansive medicines in a common group of preparations with equal composition of active substances and routs of administration [5]. The negative list are medicines that are not refundable. Thus, the costs of branded and / or innovative drugs may not be reimbursed in the presence of similar generics (with proven clinical efficacy). Often a negative list is also used to stimulate the development of the domestic pharmaceutical industry by prohibiting reimbursement of expenses for some imported drugs. Equally important is the issue of prices for medicines, which are reimbursed under insurance programs. Another mechanism that effectively regulates the consumption of medicines reimbursed under insurance programs in some countries is the joint payment of medicines. The size and type of co-payment may vary depending on the type of medication, disease, age and many other factors. According to the existing trends, the transition to drug insurance is possible in the coming years. Creation of mathematical models of insurance based on the analysis of factors explaining the use of medicines is an important task of insurance medicine and improving the quality of drug assistance and the effectiveness of the health care system. The scale of the tasks put forward for the informatization of public health requires the joint efforts of the state and business within the framework of public-private partnership with the aim of increasing the efficiency, safety and accessibility of medical services and medicines for the population of the Russian Federation. According to modern estimates, with the introduction of an automated system for the registration of medicines, it is possible to save 10% on medicine costs, which is relevant throughout the country. However, this cannot be achieved without solving a large and complex problem - the integration of databases, knowledge bases and elements of applied systems (electronic medical cards, digital medical equipment, mobile clients, disk libraries, data servers, broadband networks, etc.). Also, the proposed approach will unite and strengthen the aggregate potential of leading experts by integrating it into a single knowledge base, as well as using a set of modern methods for extracting, analyzing and forecasting them based on semantically oriented technologies in the field of large data (classification, clustering, neural networks, training, etc.). The system architecture will simultaneously provide a number of important operational qualities, such as: reliability, availability, security, fault tolerance, mobility and ergonomics. The system will also be used to calculate individual regimens of patients taking medications, including those with a narrow therapeutic range (small difference between the minimum effective dose and the maximum non-toxic dose, and also the choice of solution composition for patients receiving all their fluid and nutrition through intravenous infusions). It is known that the level of drug concentration in the blood increases when the ingested medicine is
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absorbed in the body, and then falls when the drug spreads through other tissues, then biotransformed and removed from the body. For drugs with a narrow therapeutic range (with little difference between the minimum effective and maximum safe concentration), the dose intervals and single dose should be carefully calculated to ensure drug concentration in a given range. Too little concentration will not give the desired therapeutic effect, too high will lead to side effects and, in some cases, death. The researchers developed pharmacokinetic models that represent the level of the drug in the blood as a function of the number of doses of the drug and the time they are taken, the way the medication is administered; specific pharmacokinetic parameters of the drug (e.g. duration of drug withdrawal from the body and removal from the body tissues); (for example, age, sex, and ideal body weight), as well as concomitant therapy and disease factors that affect the effects of the drug (e.g., coronary insufficiency, pneumonia, smoking, and concomitant use of phenobarbital are among the factors that affect the effect of theophylline - bronchodilator, used to treat bronchospasm spasm in bronchial asthma and pulmonary emphysema). Medical professionals use pharmacokinetic models to predict the future level of drug concentration in the blood and thus to determine the optimal regimens for therapy. Since the 1970s, Jeliff and colleagues have presented one of the first systems to assist physicians in determining dosage regimens in the use of digitalis, then described the Bayesian predictive model in which parameters of the pharmacokinetic model varied depending on the results of laboratory serum drug concentrations [6]. This model was tuned to a particular patient and thus provided a better match between the measured and predicted drug concentrations. Currently, there are computer programs that provide rapid calculation of drug concentrations using complex pharmacokinetic equations; these calculations help clinicians predict the effectiveness of drug therapy and strengthen the role of clinical pharmacotherapists in conducting pharmacokinetic consultations. Also, digital systems have been used to formulate solutions intended for intravenous infusion to patients who are thus partially or completely fed. When preparing such solutions, physicians and pharmacists must take into account a large number of factors, singly and in combination. These factors include the patient's fluid balance and calorie content, the level of dextrose (sugar) and lipid (fat) content, as well as the electrolytic balance (potassium, sodium, calcium, etc.). The preparation of nutrient solutions is particularly difficult in the treatment of newborns and other pediatric patients, since for them the mineral composition and caloric content of solutions should be high, but the volume of fluid consumed must be severely limited. Without the help of a computer, doctors and pharmacists have to manually calculate and verify recipes that must satisfy many limitations. The developed system will be able to perform many of the pharmacy functions for the dispensing and distribution of medicines. Already, there are technologies for automating most of the process of using drugs from the moment of making a therapeutic decision to taking the medicine by the patient; with its help it will be possible to use computers for routine monitoring of prescriptions to identify potential adverse reactions, to draw the attention of pharmacists to complicated or unusual appointments, as well as for automatic packaging of tablets and capsules by sachets for dispatch to the patient. The use of barcodes in pharmacies can eliminate the last significant technological obstacle for the dispensing of drugs using computer-controlled automata. Used in all supermarkets, bar-code technology is already used in a number of hospitals for marking blood samples, case histories, envelopes with X-rays. Pharmacy robots are already used in Japan, and in the US their prototypes are being tested. Another potential application of bar code technology in pharmacies is the automatic control of the stock of medical goods and computerized control over the shelf life of medicines and the write-off of overdue medical products. The use of barcodes can even reduce the number of errors in taking medications - medical professionals will be able to verify that the given medicine is correctly given to exactly this patient by scanning the patient's identification bracelet with the bar code printed on it and the label with the bar code on the medicine package. The Ministry of Health of the Russian Federation has prepared a Concept for the creation of a federal state information system for monitoring the movement of medicinal products from the manufacturer to the end consumer using labeling. Particular attention is paid to interaction with external information systems, which allows for integration with the digital system to improve the effectiveness of pharmacotherapy. The structure of external systems that carry out information interaction with components includes: information systems of federal executive bodies of the Russian Federation; information systems of manufacturers of medicines; information systems of organizations engaged in wholesale trade in medicinal products; information systems of pharmacy organizations;
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information systems of medical organizations; information systems of organizations engaged in the destruction of medicinal products. The technology of local networks and telecommunications implemented in the system also affect the pharmacy business. Automating the process of registering recipes will not only speed up their filling, but will provide an opportunity for immediate feedback from doctors to provide them with information about the effectiveness and consistency of their appointments. For example, if a doctor enters a prescription for a medicine and the computer identifies a potential drug interaction, then this information will be provided to him immediately, and not several hours later - and maybe too late. In addition, pharmacists will no longer be chained to local databases and will have quick access to national databases containing information on the prices of medicines, medicines, the use of which is paid by specific payers of medical services, as well as the criteria for optimizing the use of medicines. The system will perform processing requirements in real time, while checking the presence of potential problems in prescriptions, for example, drug interactions. Pharmacies will be able to directly connect to this system via the Internet, which will allow them to receive an immediate decision regarding the recipes they provide. This same digital technology will promote the growth of opportunities for professional communication with pharmacy computer systems. Any state pharmacist can become a participant in such a conference. The system will allow users to sign up for participation in a number of thematic teleconferences and take part in them, by contacting the university system via dial-up telephone lines. Working on their personal computer, participants will be able to view the lists of issues discussed within the framework of this thematic teleconference and send their comments to the system. Implementing systems at the treatment site, using bedside terminals to collect critical information, such as symptoms and medication data, will increase the medical component of the databases and allow for the implementation of fairly sophisticated individual drug control methods. For example, it will be possible to establish exactly which medication the patient has taken and when it happened. Detailed and accurate information about medications and symptom information are essential for evaluating therapeutic regimens, controlling the effectiveness of drug therapy, and detecting adverse drug reactions. At the present time, it became possible not only to represent any kind of information - numbers, texts, sound, images - in a digital format suitable for storage and processing in a personal computer, but also an infrastructure for its high-speed distribution. As an example, an LTE network (the standard for wireless high-speed data transmission for mobile phones and other data terminals) is present in 83 regions of Russia, and 70% of the population in the coverage zone (as of the beginning of 2016) [7]. These technologies provide an opportunity to provide instant access to a huge range of information systems using personal pocket computers, the functionality of which contains most modern mobile phones. The system will allow the implementation of mobile devices for optimization in drug provision of the population. It includes distance trade in medicines, support for the selection of pharmacotherapy methods, electronic prescriptions and appointments, electronic records in the medical history, electronic document management associated with this direction, as well as warehouse accounting systems. Rapid access to detailed clinical data and application of artificial intelligence methods to the control of drug therapy will greatly enhance the ability of the automated control system to identify potential problems in drug therapy and provide recommendations for their elimination. In addition, the continued development of pharmacological knowledge bases will have a major impact on the reform of pharmaceutical information services. Integration of such knowledge bases and automated hospital information systems will provide pharmacy workers and other medical personnel with operational access to actual information about medicines. Medical specialists will be able to receive from clinical consultation systems and expert advice on the planning of therapy. In the course of project implementation, an information system for the optimal management of medicines and medical technologies in medical organizations will be created based on the application of clinical recommendations. The system will consist of two main blocks: a knowledge base that is unified for all medical organizations, accompanied by a single scientific and methodological center and an information system for managing the turnover of medicines, integrated with other information systems, components of the Unified State Health Information System (as shown on figure 1) operating on the basis of a single knowledge base.
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Fig. 1. Unified
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State Health Information System and Digital pharmacotherapy improvement system integration scheme.
The knowledge base will be a repository of formalized knowledge, including a semantic network of medicines, algorithms and mathematical methods for processing knowledge and decision-making, methods of automated learning and the formation of rules for the derivation of solutions. Knowledge base management will be provided by an information system that provides expert work, interaction with various sources of knowledge and data, normative and reference information. The commercialization of the project is achieved through the sale of information systems for the management of drugs, in the future also through subscriber access to the knowledge base from other applications. 1.3 Conclusion Thus, the introduction of this system into commercial operation will make it possible to translate the civil circulation of medicines into a single information space and increase the effectiveness of the ongoing pharmacotherapy, and as a result, to improve the key indicators of public health. It can be confidently asserted that the list of digital solutions of such a scale ready for implementation in the organizations of the sphere of circulation of medicines is currently quite small. This creates a great growth potential, which can be realized in the shortest possible time and without significant financial costs for competition. And as a result it is a promising opportunity to increase of the effectiveness of pharmacotherapy and public health in general.
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References 1. Donald W. Light New Prescription Drugs: A Major Health Risk With Few Offsetting Advantages. Edmond J. Safra Center for Ethics Harvard University https://ethics.harvard.edu/blog/new-prescription-drugs-major-health-risk-few-offsetting-advantages 2. Lipaev V. V., Potapov AI Estimation of expenses for the development of software. - Moscow: Finances and Statistics, 1988. - 156 p. 3. Bunova EV, Buslaeva O.S. Evaluation of the effectiveness of the introduction of information systems // Bulletin of the Astrakhan State Technical University. Series: Management, Computing and Informatics, Issue 1, 2012. 4. G.Lebedev, Y.Tikhonova. Information system for pharmacotherapy method selection // International Conference on Knowledge Based and Intelligent Information and Engineering Systems, KES2017, 6-8 September 2017, Marseille, France / Procedia Computer Science. Vol.112, 2017, Pages 1658-1663. 5. A.A. Svistunov, Yu.V. Olefir, G.S. Lebedev, K.A. Koshechkin Formation of a single information space in the sphere of medicinal products circulation // Pharmateka Special issue Otorhinolaryngology 2017, p. 51-55. 6. Jelliffe, R. et al. Achieving target goals most accurately using nonparametric compartmental models and "multiple model" design of dosage regimens. Ther. Drug. Monit., V. 22, p. 346-353, 2000 7. A.A. Svistunov, Yu.V. Olefir, G.S. Lebedev, K.A. Koshechkin Telemedicine. The next stage is telepharmacy? // Electronic scientific publication (scientific and practical journal) "Social aspects of public health" N4 2017 http://vestnik.mednet.ru/content/view/849/27/lang,ru/