Umeščanje in dostop pacientov do inovativnih zdravil za zdravljenje redkih bolezni v Sloveniji

Andreja Detiček (Author), Igor Locatelli (Mentor), Mitja Kos (Co-mentor)

Abstract

Zdravstveni sistemi se ob naraščajočih stroških za zdravila soočajo z izzivom, kako zagotoviti čim boljšo in naprednejšo oskrbo svojih prebivalcev z zdravili ter ob tem ohranjati vzdržnost. Na podlagi številnih pobud strokovnjakov, pacientov in drugih organizacij je naraslo število inovativnih zdravil na različnih terapevtskih področjih, med njimi tudi na področju redkih bolezni, ki prizadenejo 5 na 10 000 oseb ali manj, a so številne. Večina redkih bolezni je resnih, kroničnih, življenjsko ogrožajočih in močno vpliva na kakovost življenja bolnika. Zdravila za zdravljenje redkih bolezni imajo tako visoko terapevtsko vrednost za bolnike s pogosto omejenimi možnostmi zdravljenja. Dokazi o učinkovitosti in varnosti omenjenih zdravil so pogosto šibkejši kot pri drugih zdravilih, njihova cena pa je običajno visoka. Odločanje o financiranju zdravil iz javnih sredstev predstavlja enega ključnih procesov umeščanja zdravila v zdravstveni sistem. Tako v Sloveniji kot v številnih drugih evropskih državah odločitve o njihovem financiranju temeljijo na vrednotenju zdravila na podlagi več meril. Cilj zdravstvenih sistemov je zagotoviti sistematičen in transparenten postopek odločanja o financiranju zdravil z upoštevanjem ključnih meril, zato se oblikujejo novi modeli meril. Ti vključujejo tudi merila, ki v slovenskem modelu meril niso vključena, kot so solidarnost, vidik družbe ter organizacija zdravstvenega sistema. V številnih državah so bili razviti novi modeli meril, zlasti za zdravila za zdravljenje redkih bolezni, ki ponekod obsegajo drugačna merila kot za vrednotenje ostalih zdravil. Dostop pacientov do inovativnih zdravil in še posebej do podskupine inovativnih zdravil za zdravljenje redkih bolezni se tako lahko zaradi različnih politik umeščanja zdravil, tudi na podlagi upoštevanja različnih meril pri odločanju o njihovem financiranju, med državami močno razlikuje. Namen doktorske disertacije je bil ovrednotiti dostop slovenskih pacientov do inovativnih zdravil za zdravljenje redkih bolezni in inovativnih zdravil za zdravljenje drugih bolezni ter ugotoviti, ali se v Sloveniji dostopa do obeh skupin inovativnih zdravil razlikujeta. V nadaljevanju smo želeli ugotoviti, katera merila so v procesu odločanja o razvrščanju in financiranju zdravil smiselna za vrednotenje zdravil za zdravljenje redkih bolezni. Na podlagi smiselnih meril smo želeli zastaviti predlog novega modela meril za vrednotenje zdravil ter ugotoviti, ali ta napoveduje oz. vodi v drugačne odločitve o financiranju zdravil za zdravljenje redkih bolezni od obstoječega. Za ovrednotenje dostopa slovenskih pacientov do inovativnih zdravil smo uporabili mednarodne podatke o volumski in vrednostni prodaji zdravil iz podatkovne baze IMS MDART (IMS Health/IQVIA). Dostop pacientov v Sloveniji smo opredelili preko primerjave dostopa s ključnimi evropskimi trgi inovativnih zdravil ob predpogoju zaznane kontinuirane uporabe v podatkovni bazi. S seznama Evropske agencije za zdravila smo opredelili reprezentativno skupino inovativnih zdravil in jih preučevali v obdobju 2007-2016 za 16 evropskih držav. Nabor zdravil za zdravljenje redkih bolezni smo povzeli s portala strokovnega združenja Orphanet in jih preučevali v obdobju 2005-2014 za 22 evropskih držav. Podatke smo obdelali s pomočjo IBM SPSS v23 in Microsoft Excel in določili naslednje mere dostopa: število zdravil v kontinuirani uporabi, čas od datuma registracije do pričetka kontinuirane uporabe, porabljena sredstva za zdravila, delež sredstev za zdravila glede na vsa zdravila in količinsko porabo v miligramih na pacienta (samo za inovativna zdravila). Dodatno smo za zdravila za zdravljenje redkih bolezni v Centralni bazi zdravil 2 poiskali obseg financiranja v Sloveniji razpoložljivih zdravil. Ključne evropske trge smo opredelili na podlagi ekonomskih kazalnikov v zdravstvu in določenih mer dostopa. V drugem delu smo oblikovali nova merila za razvrščanje in financiranje zdravil v Sloveniji na podlagi fokusne skupine v obliki polstrukturirane vodene razprave s petimi izkušenimi strokovnjaki ključnih institucij v slovenskem zdravstvenem sistemu, t.j. Zavoda za zdravstveno zavarovanje Slovenije, Javne agencije za zdravila in medicinske pripomočke, Nacionalnega inštituta za javno zdravje in Univerzitetnega kliničnega centra Ljubljana. Razpravo smo ob privolitvi udeležencev posneli z avdio snemalnikom in pripravili dobeseden transkript, ki smo ga obdelali v programu NVivo 11. Kodiranje besedila sta izvajala dva raziskovalca v treh fazah: neodvisno kodiranje obeh raziskovalcev, primerjava oblikovanih modelov meril in usklajevanje kod oz. vsebinskih sklopov, ponovitev kodiranja in končna potrditev modela. Tako smo oblikovali predlog novega modela meril za razvrščanje in financiranje zdravil. Med 619 (inovativnimi zdravili, ki so pridobila dovoljenje za promet med 2003 in 2017 pri Evropski agenciji za zdravila, je reprezentativno skupino inovativnih zdravil predstavljalo 112 zdravil za zdravljenje rakavih bolezni. Za skupino 81 zdravil za zdravljenje rakavih bolezni, registriranih med 2007 in 2016 ključne evropske trge predstavljajo Nemčija, Francija, Švedska, Norveška in Švica. Omogočajo dostop do 54-74 zdravil od 81 registriranih zdravil znotraj 3 oz. 6 mesecev po registraciji, v Franciji in Nemčiji pa zanje namenijo najvišji delež sredstev za zdravila ( ≥ 7 %). Količinska poraba je bila najvišja v Švici in Franciji (1,3- oz. 1,2-kratnik nemške porabe). Slovenski pacienti dostopajo do 53 zdravil v času 15 mesecev po registraciji, zanje je namenjenih 7,8 % sredstev za vsa zdravila, celokupna količinska poraba pa znaša 1,2-kratnik nemške, za podskupino zdravil za hematološke rake pa 2,1-kratnik nemške. Dostop slovenskih pacientov do inovativnih zdravil za zdravljenje rakavih bolezni je tako primerljiv s ključnimi evropskimi trgi glede na število zdravil, porabljena sredstva in njihovo količinsko porabo in nakazuje na vzgib umeščanja inovativnih zdravil na področju zdravljenja rakavih bolezni. Za skupino 125 zdravil za zdravljenje redkih bolezni (od tega 71 zdravil s statusom sirote), registriranih med 2005 in 2014, ključne evropske trge predstavljajo Nemčija, Švedska, Francija in Velika Britanija. Omogočajo dostop do 77-102 zdravil od 125 zdravil znotraj 3-9 mesecev po registraciji, v Nemčiji pa zanje namenijo najvišji delež sredstev za vsa zdravila (≥ 7 %). Slovenski pacienti dostopajo do 53 zdravil v času 15 mesecev po registraciji, zanje je namenjenih 8,6 % sredstev za vsa zdravila, 79 % pa jih je tudi delno ali polno financiranih iz javnih sredstev. Dostop slovenskih pacientov do inovativnih zdravil za zdravljenje redkih bolezni glede na število razpoložljivih zdravil in čas dostopa ni primerljiv s ključnimi evropskimi trgi, po porabi sredstev pa se nakazuje kot primerljiv. Dostop slovenskih pacientov do inovativnih zdravil za zdravljenje raka se od dostopa pacientov do inovativnih zdravil za zdravljenje redkih bolezni razlikuje zlasti v manjšem številu razpoložljivih zdravil za zdravljenje redkih bolezni (52 % v primerjavi z 75 % v Nemčiji razpoložljivih inovativnih zdravil). V okviru razprave o razumevanju in smiselnosti meril za razvrščanje in financiranje zdravil v Sloveniji so predstavniki ključnih institucij v slovenskem zdravstvenem sistemu menili, da je pri vrednotenju vseh zdravstvenih tehnologij smiselno uporabiti širši nabor meril, ki naj bi bila vsebini (kvalitativno) enaka za vsa zdravila, tudi za skupino zdravil za zdravljenje redkih bolezni. Bili so enotnega mnenja, da so lahko relativni prispevki posameznih meril za posamezne skupine zdravil različni glede na višino ocene skupine zdravil znotraj posameznega merila, na primer na podlagi določene lastnosti bolezni. Kot takšno skupino zdravil prepoznavajo tudi zdravila za zdravljenje redkih bolezni. Nov predlog modela meril zajema vidike koristi in tveganja zdravljenja z zdravilom za pacienta, ekonomski vidik, breme bolezni, upoštevanje zdravstvenih prioritet na podlagi družbenih vrednot, vpliv implementacije zdravila na zdravstveni sistem ter dva družbena vidika vpliva bolezni in vpliva zdravila na bolnikove svojce ali skrbnike oz. širšo družbo. Najpomembnejše vidike predstavljajo učinkovitost in varnost zdravila, kakovost dokazov o varnosti in učinkovitosti, ekonomski vidik in breme bolezni. Razliko med obstoječim modelom meril in predlogom novega modela meril predstavljajo tri popolnoma nove domene; med njimi sta v sklopu družbenega vidika dve merili, ki preusmerjata vrednotenje zdravil zgolj s koristi za pacienta na korist zdravila za širšo družbo in izpostavljata dva vpliva, t.j. vpliv bolezni in vpliv koristi zdravila na bolnikove svojce ali skrbnike oz. na širšo družbo. Po mnenju strokovnega panela novo zastavljena družbena vidika v obstoječem modelu primanjkujeta. Tretji nov vidik je vpliv implementacije zdravila na organiziranost zdravstvenega sistema. Za vrednotenje zdravil za zdravljenje redkih bolezni najbolj pomembno razliko med obstoječim modelom in novim predlogom modela lahko predstavlja potencialna vključitev etičnih vidikov na način, da se ti ne upoštevajo ločeno kot samostojno merilo, ampak se odražajo skozi zdravstvene prioritete. Etični vidik v obstoječem modelu upošteva predvsem redkost oz. resnost bolezni, v novem predlogu modela meril pa bi lahko bil upoštevan na podoben način ali pa zajet v sklopu zdravstvenih prioritet. Med najvišje zdravstvene prioritete po mnenju strokovnega panela zagotovo sodijo tiste resne bolezni, ki so razširjene, preostale zdravstvene prioritete pa naj bi po njihovem mnenju na podlagi družbenih vrednot postavili na podlagi konsenza slovenske družbe. Ob prihodnji ponovni opredelitvi zdravstvenih prioritet na podlagi reprezentativnega mnenja širše slovenske družbe te ne bi nujno razvrstile vseh redkih bolezni na enak način oz. v enaki meri in bi lahko prišlo do razlikovanja med redkimi boleznimi. V slednjem primeru predlagani model meril ne bi nujno omogočal dodatno višjega ovrednotenja vseh zdravil za zdravljenje redkih bolezni na podlagi redkosti bolezni na enak način. Ob uporabi predlaganega novega modela meril bi bila podobno kot v obstoječem modelu ob sprejemljivih stroških zdravljenja višje ovrednotena predvsem zdravila za zdravljenje redkih bolezni, ki bi izkazovala zadostno učinkovitost in varnost in ki bi bila namenjena zdravljenju redkih bolezni, ki so življenjsko ogrožajoče, dodatno pa tista zdravila, in ki močno vplivajo na samostojnost pacienta. Rezultati raziskav kažejo, da v slovenskem zdravstvenem sistemu pacientom nekoliko počasneje kot v nekaterih drugih državah omogočamo dostop do številnih inovativnih zdravil in jih v primeru umestitve v zdravstveni sistem tudi nudimo večjemu številu pacientov kot v številnih drugih evropskih državah, kar nakazuje na vzgib k umeščanju inovativnih in naprednih možnosti zdravljenja. Predlog novega modela meril daje usmeritve za vrednotenje in odločanje o razvrščanju in financiranju zdravil v Sloveniji v prihodnje in predstavlja izhodišče za oblikovanje prenovljenega uradnega modela meril v slovenskem prostoru. Hkrati predlagana nova merila predstavljajo zgled za zdravstvene sisteme drugih držav, ki temeljijo na podobnih vrednotah.

Keywords

zdravila;vrednotenje;merila;financiranje;zdravstveni sistem;

Data

Language:	Slovenian
Year of publishing:	2019
Typology:	2.08 - Doctoral Dissertation
Organization:	UL FFA - Faculty of Pharmacy
Publisher:	[A. Detiček]
UDC:	616-039.4-085(497.4)(043.3)
COBISS:	301427968
Views:	105
Downloads:	1
Average score:	0 (0 votes)
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Other data

Secondary language:	English
Secondary title:	Reimbursement decision-making and patient access of innovative medicines for rare diseases in Slovenia
Secondary abstract:	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.
Secondary keywords:	Redke bolezni;Disertacije;Zdravljenje;Originatorska zdravila;Dostopnost;Slovenija;
Type (COBISS):	Dissertation
Thesis comment:	Univ. v Ljubljani, Fak. za farmacijo
Pages:	220 str.
ID:	15595310