Due to increasing medicine expenses, the healthcare systems are challenged by how to enable the best and most advanced health care and medicines to their inhabitants while maintain system sustainability. Several incentives by experts, patients and other organizations have generated the increase of the number of innovative medicines in various therapeutic fields, also for rare diseases which affect 5 in 10 000 people or less and are numerous. The majority of rare diseases are severe, chronic, life-threatening and severely affect quality of life of the patient. Therefore, medicines for rare diseases possess high therapeutic value for the patients with often limited treatment options. The efficacy and safety evidence of these medicines are often weaker than in other medicines while their price is usually higher. Reimbursement decision-making enables medicine funding from public resources and therefore represents one of the crucial processes in placing the medicine into the healthcare system. In Slovenia and in many other European countries reimbursement decisions are based on medicine evaluations using multiple criteria. Healthcare systems’ aim is to ensure a systematic and transparent medicine reimbursement decision-making process by including the crucial criteria, which has resulted in formation of several new criteria models abroad. These also include criteria that are currently not considered in the Slovenian criteria model, e.g. solidarity, social aspects, and healthcare system organization. New criteria models have been developed in several countries, especially for medicines for rare diseases, which in some countries comprise different criteria than those used for evaluation of other medicines. Patient access to innovative medicines and especially to innovative medicines for rare diseases could largely vary among the countries due to differences in decision-making policies and in using different sets of reimbursement decision-making criteria. The aim of the doctoral thesis was to evaluate the access of the Slovenian patients to innovative medicines for rare diseases and to other innovative medicines, and to determine whether the patient access to both groups of innovative medicines in Slovenia differs. Further, the aim was to explore which decision-making criteria seem reasonable for evaluating medicines for rare diseases in the medicine reimbursement decision-making process in Slovenia. Based on these reasonable criteria, our purpose was to build and propose a new medicine evaluation criteria model and to discover if the new model predicts or leads to different reimbursement decisions for medicines for rare diseases than the existing one. To evaluate the access of the Slovenian patients to innovative medicines, the international data on volume and value medicine sales from the IMS MDART (IMS Health/IQVIA) database were used. Patient access in Slovenia was determined by comparison with key European innovative medicine markets and based on detection of continuous medicine use in the database. Using European Medicines Agency’s list of medicines, the representative group of innovative medicines was defined and studied during 2007-2016 in 16 European countries. The group of medicines for rare diseases was formed following the rare disease expert portal Orphanet and studied during 2005-2014 in 22 European countries. The data were analysed using IBM SPSS v23 and Microsoft Excel and the following patient access measures were determined: the number of medicines in continuous use, the time between registration date and the start of continuous use, medicine expenditure, the proportion of total medicine expenditure, and quantitative use in milligrams per patient (only for the group of innovative medicines). Additionally, medicines for rare diseases were searched for in the local Central medicine database 2 to determine the extent of reimbursement for medicines available in Slovenia. The key European markets were defined according to the healthcare economic markers and observed patient access measures. In the second part, we built a new proposition of the reimbursement decision-making criteria model for reimbursement decision-making process in Slovenia. The model was based on a focus group discussion in a form of a semi-structured guided discussion with five experienced experts from four most representative Slovenian healthcare institutions, i.e. Health Insurance Institute of Slovenia, Agency for Medicinal Products and Medical Devices of the Republic of Slovenia, National Institute of Public Health and University Medical Centre Ljubljana. The discussion was audio recorded upon participants’ approval and the verbatim transcript was prepared and analysed using NVivo 11. The coding of the transcript was performed by two researchers in three phases: independent coding by both researchers, a comparison of both criteria models while codes/contents were adjusted, second coding and final confirmation of the criteria model. In that way we formed a new proposition of decision-making criteria model for medicine reimbursement decision-making. Out of 619 original (innovative) medicines that were approved by the European Medicines Agency between 2003 and 2017, the representative group of innovative medicines included 112 anticancer medicines. The key European markets concerning access to the subgroup of 81 anticancer medicines approved between 2007 and 2016 were Germany, France, Sweden, Norway, and Switzerland. These countries enable access to 54-74 medicines of 81 approved medicines within 3-6 months after approval. Also, in France and in Germany, the proportion of the total medicine expenditure spent on anticancer medicines was the highest (≥ 7%). The quantitative use of these medicines was the highest in Switzerland and in France (1.3 and 1.2-fold German use, respectively). The Slovenian patients access 53 medicines within 15 months after approval, while 7.8% of total medicine expenditure is used for anticancer medicines. In addition, the total quantitative usage was 1.2-fold German and 2.1-fold German for the subgroup of medicines used for Haematological Malignancies. Patient access to innovative anticancer medicines in Slovenia is therefore comparable to key European markets according to the number of medicines, medicine expenditure and their quantitative use and this demonstrates the intention for enabling access to innovative medicines in cancer treatment. The key European markets concerning access to the group of 125 medicines for rare diseases (of which 71 had orphan status) approved between 2005 and 2014 were represented by Germany, Sweden, France, and United Kingdom. These countries enable access to 77-102 medicines of 125 medicine within 3-9 months after approval. Also, in Germany the proportion of the total medicine expenditure spent on anticancer medicines was the highest (≥ 7%). The Slovenian patients access 53 medicines within 15 months after approval, while 8.6% of total medicine expenditure is used for medicines for rare diseases and 79% are partially of fully reimbursed from public resources. Patient access to innovative medicines for rare diseases in Slovenia is not comparable to key European markets according to the number of medicines and time of access but seems comparable according to medicine expenditure. Patient access to innovative anticancer medicines in Slovenia differs from the patient access to innovative medicines for rare diseases especially in fewer available medicines for rare diseases (52% versus 75% innovative medicines available in Germany).
The discussion with experts from the most representative healthcare institutions about understanding and reasoning of the medicines reimbursement decision-making criteria revealed that the experts believe that all health technologies should be evaluated using multiple criteria which should be identical (qualitatively) for all medicines including medicines for rare diseases. They unanimously argued that relative contributions of criteria could differ among evaluations of different groups of medicines due to a different score of the medicine group based on the characteristics of the disease, such as medicines for rare diseases. The new proposed criteria model includes aspects, such as medicine benefit and harm for the patient, economic aspect, disease burden, healthcare priorities based on societal values, the impact of medicine implementation on healthcare system and two societal aspects – impact of disease and medicine impact on patient family or caregivers and the broader society. The most important aspects according to the experts’ opinion are medicine efficacy and safety, quality of efficacy and safety evidence, economic aspect and disease burden. The newly proposed criteria model differs from the existing one in three effectively new domains; among those there are two criteria expressing the societal aspect which redirect the medicine evaluation from regarding only benefits for the patient to regarding benefits of the medicine for the society by including the impact of the disease and the impact of the medicine on patient family or caregivers and broader society. The experts believe that the existing medicine reimbursement decision-making criteria model lacks the two societal aspects. The third new aspect is the aspect of medicine implementation and its effect on the healthcare system organization. In the new proposed criteria model, the greatest difference for evaluating medicines for rare diseases represents the potential inclusion of the existing ethical aspect under healthcare priorities. Within the existing criteria model, the ethical aspect considers disease rareness or severity, while in the newly proposed criteria model, it could be either included in the same manner or it could be joined under and expressed through the healthcare priorities. According to the opinion of the expert panel, severe diseases that are very common should be considered one of the highest healthcare priorities while other diseases should be prioritized according to broader societal consensus. In the potential future redefinition of the healthcare priorities according to the representative opinion of the broader Slovenian society, healthcare priorities wouldn’t necessarily include all rare diseases in the same manner and there could be some differentiation between different rare diseases. In that case, all medicines for rare diseases would not be assessed with a higher score based on the rarity of the disease in the same way. Using the newly proposed criteria model, medicines for rare diseases with acceptable costs of treatment and stronger efficacy and safety evidence or medicines for life-threatening rare diseases would be evaluated with a higher score, as in the existing model, and would be evaluated even higher if the disease strongly affected patient independence of family’s or caregivers’ assistance.
The results of our studies demonstrate that patients in the Slovenian healthcare system access innovative medicines more slowly than in other countries while they are enabled access to numerous innovative medicines which are available and offered to larger number of patients than in several other European countries. This also demonstrates the intention for enabling access to innovative medicines and advanced treatment possibilities. The new proposition of medicine reimbursement decision-making criteria model offers guidance in further medicine evaluations and reimbursement decision-making in Slovenia and represents the ground for building the renewed official criteria model. Simultaneously, the proposed new criteria represents an example for other healthcare systems that are founded on similar values.
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